Methods and devices for conduit occlusion

ABSTRACT

The present invention comprises systems, methods and devices for the delivery of compositions for occluding or of elements for opening conduits. The implantable occlusive material may be delivered pre-formed or in situ cured and, may be a resorbable or degradable material that supports tissue ingrowth or wound healing or a similar response that replaces the cured occlusive material leaving little or no original occlusive material in place. The delivery system is positioned to allow for placement of the occlusive material into the body conduit. Use of delivery systems, methods and devices for re-opening an occluded body conduit are also included.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.13/684,546 filed Nov. 25, 2012, which is a continuation of U.S. patentapplication Ser. No. 13/285,908 filed Oct. 31, 2011 (now U.S. Pat. No.8,336,552), which is a continuation of U.S. patent application Ser. No.12/240,738 filed Sep. 29, 2008 (now U.S. Pat. No. 8,048,101), which is acontinuation-in-part of U.S. patent application Ser. No. 11/065,886filed Feb. 24, 2005 (now U.S. Pat. No. 8,048,086), which claims thepriority of U.S. Provisional Patent Application 60/547,491 filed Feb.25, 2004, and claims the priority of U.S. Provisional Patent Application60/587,604 filed Jul. 13, 2004, each of which is herein incorporated byreference in its entirety.

TECHNICAL FIELD

The present invention relates to methods and devices for occludingconduits. In particular, the present invention is directed to methodsand devices for delivery of compositions that lead to occlusion ofconduits and for later re-opening of such occluded conduits.

BACKGROUND OF THE INVENTION

In the medical and research fields, there are many clinical situationswhere it is desired or necessary to stop the passage, flow or transferof substances within a body tube or conduit by causing an occlusion orblockage. It is often desirable for the occlusion to be re-opened at alater time. Unfortunately, many occlusion techniques are often harmfulor potentially harmful and are not reversible to accommodate changes inthe needs or desires of patients.

One area that has a need for permanent and possible subsequentreversible occlusion of a body tube is the control of fertility. Overthe last 50 years, the world has experienced the highest rates ofpopulation growth and the largest annual population increases recordedin history. Women account for over 50% of the world's population andplay a critical role in family health, nutrition, and welfare. One ofthe most significant areas in need of attention and innovation inwomen's healthcare is that of contraception, where the reproductive agedwoman is currently faced with sub-optimal alternatives.

Over the past 20 years, couples in every world region have adoptedcontraception with increasing frequency as a means of regulating thetiming and number of children. However, in the less developed countriesthere are still a substantial number of women, who wish to controlfertility but are not presently using contraception. Many governmentsworldwide are intervening with policies to provide access tocontraceptive methods to control over-population. In 2000, it wasestimated that 123 million women did not have access to safe andeffective means of contraception. Therefore, the potential for asuitable contraceptive system has widespread implications for the worldpopulation.

Today there are several contraceptive options available, althoughcurrently available options are associated with specific limitations.Some contraceptive options include surgical intervention, such as tuballigation for female sterilization and vasectomy for male sterilization,both of which are invasive and considered non-reversible. Other optionsavailable to women are hormonal contraceptives, which are not suitableor safe for a number of women. Further options include intrauterinedevices that may have significant side effects. The ideal contraceptivesystem is one that would provide an effective, reversible, or possiblyreversible, non-hormonal, non-surgical, easy to deliver, office-basedsolution that does not require anesthesia, patient compliance, orspecial equipment, and does not leave a foreign body in place long-term.None of the current options meets these requirements.

The most widely utilized method of permanent contraception is tuballigation or female surgical sterilization. There are a number of womenwho are not candidates for surgery due to excessive weight or othermedical conditions. Further, there are a number of major drawbacksassociated with tubal ligation. The procedure is permanent and invasive,requires general anesthesia, has a long recovery time, and can result inpost-tubal ligation syndrome. Post-tubal ligation syndrome occurs whenthe surgeon closing the fallopian tube inadvertently damages or destroysblood vessels to the ovaries causing post-menopausal symptoms ofabnormal bleeding, memory loss, confusion, mood swings, and lack of sexdrive. In addition, a recent study has found that of all the hormonaland non-hormonal methods of birth control, tubal sterilization has thegreatest association with development of functional ovarian cysts.Further, women who undergo tubal ligation frequently express regret orseek reversal. Reversal of tubal ligation, when attempted, is difficult,costly, and frequently unsuccessful.

On the other end of the spectrum, the most widely utilized method ofnon-surgical contraception is the administration of hormonal drugs, suchas implanted hormones or birth control pills. This method ofcontraception is effective only so long as hormones are administered orbirth control pills taken according to a specific regimen. Althoughwidely used, this method of contraception is not suitable or safe forall women. In addition, there is a high failure rate resulting inunintended pregnancies due to patient non-compliance with the dailyregimen of taking pills.

One reversible contraceptive device currently available is theintrauterine device (IUD). There are an estimated 85 to 100 millionwomen worldwide using this method, substantiating the importance ofreversibility. However, given the possible health risks associated withIUDs and patient reluctance to have a foreign body in place for anextended period of time, fewer than 1 million women in the U.S. use thismethod, and many manufacturers have ceased distribution of thesedevices. The health risks include unplanned expulsion requiring removaldue to excessive pain or bleeding, pelvic-inflammatory disease,permanent infertility, ectopic pregnancy, miscarriage and even death.

While the currently available compositions and methods for contraceptionrepresent a significant advancement in the art, further improvementswould be desirable to provide safe, effective and reversiblenon-surgical devices, compositions, and methods for preventingpregnancy. It would be beneficial if these devices, compositions andmethods provided an effective, non-hormonal, non-surgical, easy todeliver, office-based solution that did not require anesthesia orpatient compliance with a daily regimen. It would be further beneficialif these devices, compositions and methods did not require specialequipment to undertake a contraceptive procedure or require a foreignbody remaining in place over a long period of time. It would be furtherbeneficial if these devices, compositions and methods were suitable toreversal. Some or all of these advantages of an ideal contraceptivesystem are provided by the devices, systems, compositions and methods ofthe present invention.

SUMMARY

The present invention comprises methods, systems, and devices for thedelivery of compositions for the occlusion of conduits. In particular,the present invention comprises methods, systems, and devices for theocclusion of conduits in humans or other animals. The devices of thepresent invention are used to deliver compositions comprising materialsthat occlude the conduit. The conduit may be a naturally occurringconduit such as a tube or vessel in the body or may be a conduit thathas been introduced in the body such as a medical device or throughsurgical means. The occlusive material may be a permanent implant or maybe a material that is degraded or resorbed by the body and allows fortissue ingrowth or wound healing response or similar response tomaintain the occlusion.

The present invention also comprises delivery systems, methods, anddevices for reversing the occlusion. The occlusion may be reversed byremoval of implant materials or tissue ingrowth that are blocking theconduit, by creating a channel through the occlusion, or by creating anew channel around the occlusion.

One aspect of the present invention comprises delivery systems, methodsand devices for occlusion of fallopian tubes and reversal of theocclusion. One embodiment of this aspect is a method that comprisesintroduction of a delivery device system for delivery of occlusivematerial to one or both fallopian tubes without the necessity to remove,reinsert, or substantially reposition the delivery device. Such a devicemay be sized for each recipient by pre-visualization of the anatomy ofthe recipient. The implanted occlusive material may be permanent or maybe degraded or resorbed by the body and replaced by ingrowth of tissueor wound healing or similar type response. Reversal of such occlusioncomprises a device that is capable of removing the occlusive material.In another embodiment, reversal of conduit occlusion comprises a devicethat is capable of forming a channel through or around the material oringrown tissue. Reversal of conduit occlusion may further compriseplacement of devices, such as stents, to maintain the re-opened channel;these methods of maintaining the re-opened conduit are also performedthrough the use of the delivery device.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1A shows an embodiment of a delivery device for the transcervicaldelivery of occlusive material.

FIG. 1B shows an embodiment of a double lumen catheter.

FIG. 1C shows an embodiment of a cartridge component containing aflowable material, which includes, but is not limited to occlusivematerial or balloon distension material.

FIG. 2A shows a step in an embodiment of a method of the delivery systemfor deploying and using a delivery device wherein the introducer isinserted through the cervix.

FIG. 2B shows a step in an embodiment of a method of the delivery systemfor deploying and using a delivery device wherein two double lumencatheters are deployed contralaterally within the uterine cornua.

FIG. 2C shows a step in an embodiment of a method of the deliverysystem, wherein each catheter is retracted and the operator begins towithdraw the introducer shaft from the uterus.

FIG. 3A shows an embodiment of a delivery system, wherein the deliverycatheters are shown partially extended.

FIG. 3B shows a portion of the delivery system from FIG. 1A wherein theintroducer tip and partially extended catheters are shown in greaterdetail.

FIG. 3C shows an internal view of the delivery system from FIG. 3A.

FIGS. 4A-C show an embodiment of a delivery device stabilizer and itsplacement within a body. 4A shows an embodiment of a delivery devicestabilizer prior to placement in the body. 4B shows the delivery devicestabilizer in place, prior to expansion of the expandable portion. 4Cshows the expandable portion expanded.

FIG. 4D shows an embodiment of a delivery device stabilizer that isslidable on the introducer shaft and incorporates an expandable portion,that is shown unexpanded.

FIG. 4E shows an embodiment of a pre-formed delivery device stabilizerthat is slidable on the introducer shaft.

FIG. 4F shows an embodiment of a delivery device stabilizer mechanismthat is slidable on the introducer shaft and incorporates a cup-shapedbase that fits over the cervix.

FIG. 4G shows the interaction of the delivery device stabilizer shown inFIG. 4F with outer face of the cervix.

FIG. 5A-D shows a cervical clamp and its placement. FIG. 5A shows anembodiment of the delivery device in position in a body, incorporating acervical clamp. FIG. 5B shows an embodiment of the delivery device inposition in a body with the cervical clamp in position. FIG. 5C showsaspects of an embodiment of a cervical clamp. FIG. 5D shows aspects ofan embodiment of a cervical clamp.

FIG. 6A-F shows embodiments of methods and devices for opening ofocclusions. FIG. 6A shows an embodiment of delivery of one or moresolutions that degrade and remove the occlusion. FIG. 6B shows anembodiment of use of a guide wire or catheter to open the occlusion.FIG. 6C shows an embodiment of use of an expandable member, such as aballoon, to open the occlusion. FIG. 6D shows an embodiment of use of acutting or debriding member to open the occlusion. FIG. 6E shows anembodiment of an energy device to open the occlusion. FIG. 6F shows anembodiment of the conduits after opening.

FIG. 7 shows an embodiment of a delivery device having a single exitport for the transcervical delivery of occlusive material.

FIG. 8A shows a step in an embodiment of a method of the delivery systemfor deploying and using a delivery device having a single exit portwherein the introducer is inserted through the cervix.

FIG. 8B shows a step in an embodiment of a method of the delivery systemfor deploying and using a delivery device having a single exit port,wherein one double lumen catheter is deployed within the uterine cornua.

FIG. 8C shows a step in an embodiment of a method of the delivery systemhaving a single exit port, wherein the catheter is retracted and theoperator rotates the Introducer to target the untreated fallopian tubeor duct.

FIG. 8D shows a step in an embodiment of a method of the delivery systemhaving a single exit port, wherein a catheter, either the originalcatheter used in an earlier step, or a new catheter, is deployed withinthe uterine cornua of the side that was not treated previously.

FIG. 8E shows a step in an embodiment of a method of the delivery systemhaving a single exit port, wherein the catheter is retracted and theoperator begins to withdraw the device from the uterus.

FIG. 9A shows an embodiment of a fused two catheter embodiment where theexterior of the catheter bodies are fused or joined together partially,so that the fused catheter bodies traverse the introducer shaft lumen asa unit.

FIG. 9B, B1-6 shows embodiments of a cross section view of theintroducer shaft lumen with a single lumen or multiple dual lumens,wherein the septum forming two lumens is constructed of a solid, rigid,semi-rigid or flexible material.

DETAILED DESCRIPTION

The present invention comprises delivery systems, methods and devicesfor occluding conduits, and methods, systems, and devices for reversingocclusions in conduits. The present invention comprises delivery systemsand methods for occluding conduits in the body through the placement ofocclusive material using a delivery device. One aspect of the presentinvention comprises occluding conduits permanently. In another aspect,the present invention comprises reversibly occluding conduits. Yetanother aspect of the present invention comprises methods, deliverysystems and compositions to occlude the fallopian tubes of a femalemammal, and methods and systems to re-open such occlusions. A furtheraspect of the invention comprises methods, delivery systems, andcompositions to occlude the vas deferens of a male mammal, and methodsand systems to re-open such occlusions. Methods, systems andcompositions of the present invention may be used in embodiments thatpermit non-surgical, office-based permanent or reversible sterilization.

The present invention comprises methods for occluding conduits,particularly conduits found in human or other animal bodies. Suchconduits may exist naturally in the body or be present because ofdisease, damage, placement of medical devices or surgical means.

As used herein, the term “conduit” shall refer to any tube, duct, orpassage, whether natural or synthetic, which carries gas, fluids orsolids in a biological system.

As used herein, “occlude” refers to blocking, partially or fully, thetransport of gas, fluids, or solids through a conduit. The term“occlusion,” as used herein, refers to blockage within a conduit whereinsuch blockage results in partial restriction or complete interruption ofthe transport of gas, fluids, or solids through the conduit. As usedherein. “occlusive material” refers to a composition that is capable ofoccluding a conduit by effecting an occlusion therein. As used herein,occlusive or occluding material means the initial composition that isplaced or inserted into the conduit, as well as the composition, whetherthe physical, biological, or chemical nature of the composition haschanged or not, that is in place in the conduit and provides for theinterruption of flow through the conduit. The meaning of the term can bedetermined from its use in the sentence. Occlusive compositions,occlusion compositions, occlusive materials and occlusion materials areterms used interchangeably herein.

As used herein, occlusive material comprises any natural or syntheticcompositions or any combination of natural and synthetic compositionsthat can be placed at the desired site in the conduit using the deliverysystems of the present invention. Occlusive materials of the presentinvention may comprise materials that are fluid, semi-solid, gels,solids, and combinations thereof. The occlusive materials may furthercomprise a pre-formed material that is of a shape or size that occludesthe conduit or may be a material that will take on a form or shape orsize to occlude the conduit. Occlusive materials may further comprisecompositions that cure in situ at the desired site in the conduit. Theocclusive compositions may further comprise materials that polymerize insitu, wherein the polymerization may be initiated either at the site ofinterest in the conduit or prior to placement at the site. Occlusivecompositions may further comprise combinations of two or more of any ofthe foregoing materials. Disclosed herein are exemplary compositions andmaterials suitable for use as occlusive compositions.

As used herein, “cure” means a change in the physical, chemical, orphysical and chemical properties of the occlusive material followingplacement or insertion at the desired site in a conduit.

As used herein, visualization or imaging refers to all forms of imagingthat do not require the use of ionizing radiation or directvisualization such as by hysteroscopy. Examples of imaging include allforms of ultrasound or magnetic resonance imaging, which areincorporated within the scope of this definition.

As used herein, the term “delivery system” comprises all componentsnecessary to deliver an occlusive material or all components necessaryto open an occlusion, and may comprise an introducer, delivery device orcatheter(s), combinations thereof, occlusion elements or elements foropening an occlusion, and any other components necessary for the fullfunctioning of the delivery system.

In general, the methods of the present invention comprise administrationof delivery systems that deliver compositions that are capable ofoccluding conduits. The delivery systems comprise devices that arecapable of delivering occlusive compositions to the desired site.Disclosed herein are exemplary methods, delivery systems, andcompositions for occlusion of conduits of the reproductive tracts ofmammals. Such methods and compositions can be used in otherphysiological systems and biological sites of humans or other animals,and delivery systems for such biological sites are contemplated by thepresent invention.

The present invention comprises methods for opening, generally there-opening, of occluded conduits. The methods comprise elements forremoval of the occlusion, including removal of occluding compositions orfor formation of openings or channels through or around one or moreoccluded regions. Elements for removal include, but are not limited to,physical withdrawal of the occluding composition, destruction of theoccluding composition using physical, chemical or biological methods,canalization of the one or more occluded regions, and placement of newconduits, such as stents or bypass materials to restore functionality tothe formerly occluded region. Disclosed herein are exemplary methods,delivery systems and compositions for removal of the occlusion ofconduits of the reproductive tracts of mammals to restore fertilityfunctionality. Such restorative methods and compositions can be used inother physiological systems and biological sites of humans or otheranimals, and delivery systems for such biological sites are contemplatedby the present invention.

One aspect of the present invention comprises methods of contraceptionfor mammalian females that use ultrasound visualization of a deliverysystem that delivers an occlusive composition to a target site, forexample, from the cornual aspect of the uterus into each fallopian tube,wherein the composition is capable of creating a blockage in eachfallopian tube.

A further aspect comprises using the delivery system to implantocclusive material. One aspect comprises methods that use ultrasound forvisualization and positioning of the device and monitoring and/orconfirming the placement of the composition when an ultrasound visiblecomposition is used. A method comprises introduction of the device,including inserting the shaft of the introducer through the cervix untilthe atraumatic tip contacts the uterine fundus as determined byvisualization such as ultrasound or through the sensation of theoperator. When the tip is appropriately placed, optionally, the operatormay engage a member that aids in stabilizing the delivery device,referred to herein as a delivery device stabilizer. For example, thismember may be a depth stop or uterine length marker, a member whichindicates that the tip is in position and the introducer shaft shouldnot be introduced any further, and includes, but is not limited to,other delivery device stabilizers such as those shown in FIGS. 4 and 5,or more than one member that aids in stabilization. With the introducerin position, at least one double-lumen balloon catheters is introducedthrough an introducer lumen until it exits the exit port of the lumen inthe shaft of the introducer, for example as shown in FIG. 2, and the tipof the catheter is located within the uterine cornua as determined byultrasound or by sensation of the operator, or both. The inventioncomprises methods and devices, for example, as shown in FIG. 8, whereinwhen the introducer is in position, a catheter, such as a double-lumenballoon catheter, is introduced through an introducer lumen until itexits the single exit port and enters the uterine cornua, which may bedetermined by sensation of the operator (by feel) or by ultrasound, orby a combination of ultrasound and feel.

A further aspect of the present invention comprises methods wherein atleast one catheter undergoes the following steps. At a proximal end ofthe catheter, one end of the catheter which is near the housing anddistant from the delivery end of the catheter, a cartridge containingballoon distension medium is connected to the balloon fitting, thestopcock is opened, and the distension medium is delivered to effectinflation of the balloon positioned at the delivery end of the catheter.The stopcock is then closed and the cartridge is disconnected from thefitting or is automatically held inflated by a mechanism in theintroducer housing. At a proximal end of the catheter, a cartridgecontaining the occlusive composition is then connected to the deliverycatheter fitting or engaged into the introducer housing, the material isdelivered through the catheter and out of the delivery end of thecatheter that is at or adjacent to the delivery site. The material maybe delivered directly to the target site or may move from the deliverysite to the target site location, and the material cures to form theocclusion. Once the material has at least partially cured into anocclusion, the balloon is deflated or it can be immediately deflated ordeflated after a period of time. A catheter is then retracted until itis housed within the introducer shaft or fully removed from theintroducer. Depending on the delivery device or method, a new cathetermay be provided through the introducer, and the procedure is repeatedfor another conduit.

Following activity by one or more catheters, if necessary, the deliverydevice stabilizer is disengaged. The delivery system is then withdrawnfrom the patient leaving only the occlusion in place. The occlusivematerial may be delivered sequentially or simultaneously to the twofallopian tubes. The device is designed for delivery of occlusivecompositions to at least one of two separate sites with minimal to norepositioning and without removal of the device, including theintroducer, until the procedure is complete. One or both of the deliverycatheters may be retracted into the introducer without repositioning orremoval of the entire device.

Yet another aspect of the present invention comprises a delivery systemfor implantation of the occlusive composition into the fallopian tubescomprising a delivery device comprising an introducer with one or twolumens, or more lumens, optionally one or more delivery devicestabilizers, a housing element which may function as a handle if needed,elements for attachment or incorporation of one or more containers ofballoon distension medium and the occlusive composition, and at leastone catheter for delivery of the occlusive composition. The at least onecatheter may comprise an end structure, which is a balloon or othersimilarly functioning member that may function to hold the catheter inposition, prevent leakage of the material from the target site orperform both of these functions or others. The occlusive composition maybe mixed prior to delivery and then delivered from the container throughat least one catheter to one or more target sites.

One aspect of the present invention comprises a delivery systemcomprising an introducer, one or more catheters wherein each may have adistinct function or design, and one or more cartridge componentswherein each cartridge may have a distinct design and contain a distinctmaterial.

Now referring to FIG. 1A, an exemplary embodiment of an introducer isshown comprising the following subcomponents: the introducer tip (1)which is shaped for atraumatic insertion through the cervix to bepositioned at the uterine fundus; the introducer shaft (3), generally astructure which may be cylindrical or ellipsoidal in nature, whichcontains two introducer shaft catheter lumens each with an exit port(2). The lumens (not shown) traverse the interior length of the shaftand have openings for insertion of a catheter into the shaft and for thecatheter to exit the shaft; a delivery device stabilizer (4) which inthis example indicates the position of the tip relative to the point ofentry, which may be measured based on markings along the shaft and whichmay further serve to hold the introducer in position; a housing (5)which may function as a handle and have an ergonomic design for grippingby the operator; and a pair of catheter insertion holes (6) throughwhich the delivery catheters can be inserted into the introducer andguided to the introducer shaft catheter lumen exit port (2). Thedelivery device stabilizer (4) shown in this example is a depth stop oruterine length marker.

FIG. 1B shows a delivery catheter for delivery of occlusive material,said catheter comprising the following subcomponents: the delivery end(7) of the catheter through which the occlusive material is delivered tothe target site; an end structure (8), which may be a balloon, that mayhold the catheter in position and may prevent leakage of the occlusivematerial away from the target; the shaft of the catheter (9) which, inthis figure, features a pre-formed curve designed to aid in movement ofthe delivery end of the catheter from the introducer shaft into thecornual aspect of the uterus, and includes two lumens, one for inflationof the balloon and one for delivery of the occlusive material; abifurcation (10) of the catheter lumens; a fitting (11) that mates witha cartridge that contains flowable material to be delivered, such as theocclusive material; and a fitting with a stopcock (12) that mates with acartridge that contains material to be delivered, such as distensionmedia for inflation and deflation of the balloon. One aspect of thepresent invention comprises a delivery catheter that is a double lumendelivery catheter. It should be understood that the delivery cathetermay comprise a number of features and designs known in the art forcatheters and that would be useful for the function of the deliverysystem. In one embodiment of the present invention, the one or morecatheters are disposed within the hollow single or multi lumenintroducer shaft. The catheters of the present invention may be singlelumen or dual lumen catheters, or other catheters that would function inthe present invention. One aspect of the invention comprises a stopcockis used to prevent leakage of the balloon distension medium afterplacement. It should be understood that other devices, such as a valveor diaphragm, including a self-sealing diaphragm, may also serve thesame function and be useful in obtaining and maintaining inflation ofthe balloon of the present invention.

FIG. 1C shows a cartridge (14) which may contain a flowable material(16) wherein the cartridge component comprises the following aspects:the tip of the cartridge (15) that mates with the delivery catheterfitting (11) or a fitting with stopcock (12) as required; the barrel ofthe cartridge (17); a plunger (18) that fits with the barrel of thecartridge (17) so as to form a seal to prevent back-flow of flowablematerial, said plunger allowing the operator to deliver the flowablematerial; and a flowable material (16), wherein the flowable materialmay comprise occlusive material or distension media.

Now referring to FIGS. 2A-2C, wherein a schematic is shown of anexemplary embodiment of a method for deploying and using the exemplarydelivery system shown in FIG. 1 to effect an occlusion in at least onefallopian tube of a mammal. It should be understood that not all stepsneed be performed in every deployment. Further, it should be understoodthat additional steps may be added as determined by one skilled in theart as necessary to increase performance, efficacy, or comfort of thepatient undergoing the method depicted in FIG. 2.

In FIG. 2A, the operator holds the introducer housing (5) and insertsthe shaft of the introducer (3) through the cervix (20) until theatraumatic tip (1) contacts the uterine fundus (19) as determined bytactile feel, visualization such as ultrasound, or a combination of bothtactile feel and visualization. When the atraumatic tip (1) isappropriately placed, the introducer shaft lumen exit ports (2) arelocated such that the openings are directed toward the uterine cornua(24). Following contact of the atraumatic tip (1) with the uterinefundus (19), the delivery device stabilizer (4) is moved into position.In one embodiment, the delivery device stabilizer (4) may comprisecomponents or structures that function to ensure that the operatormaintains a fixed position of the introducer shaft, for example forpreventing uterine perforation, as well as maintaining the position ofthe shaft catheter lumen exit ports (2) throughout the procedure. Inanother embodiment, the delivery device stabilizer (4) may comprisecomponents or structures to provide a depth stop mechanism or uterinelength marker to the delivery device. In still another embodiment, thedelivery device stabilizer comprises components or structures to providea depth stop mechanism or uterine length marker and stabilization to thedelivery device.

FIG. 2B depicts the use of the delivery system for the introduction ofan in situ curing flowable occlusive material. With the introducer inposition, the operator moves each of two double-lumen catheters througha catheter insertion hole (6) through the introducer shaft lumens untileach catheter exits the introducer shaft lumen exit port (2), and thedelivery end (7) of the catheter is located within the uterine cornua(24) as determined by the operator's tactile feel, —imaging such asultrasound, or a combination of feel and imaging. An exemplaryembodiment of a double lumen catheter is described in FIG. 1B.

Once the delivery end (7) of the catheter is positioned within theuterine cornua (24), the catheter position may be maintained by alocking mechanism which may be attached to the housing (5) at or nearthe catheter insertion hole (6), at another location within housing (5),or by a mechanism that is separate from housing (5) and which serves tograb, clamp, hold or otherwise stabilize the catheter such that it doesnot move and such that the delivery end remains in the target location.In another aspect of the invention, inflation of the balloon asdescribed below is sufficient to maintain position of the catheter, andno additional locking mechanism may be required.

A cartridge (14) containing balloon distension medium (22), which hasbeen previously prepared or mixed if such mixing is necessary, is thenfitted to a fitting with a stopcock (12), the stopcock is opened, andthe distension medium (22) delivered to effect inflation of the endstructure (8) which is a balloon in the figure. Distension medium maycomprise any flowable or liquid material suitable for inflation of theend structure (8) which is a balloon in the figure, such material beingchemically compatible with the material of the end structure (8) whichis a balloon in the figure and may be biologically compatible in theevent distension medium is introduced into the uterine cavity orfallopian tubes. Exemplary distension media include, but are not limitedto, air and sterile isotonic saline solution. Following inflation of theend structure (8) which is a balloon in the figure, the stopcock is thenclosed, the cartridge disconnected from the fitting (12), and theprocedure repeated to inflate the balloon on the contralateral side. Theballoons may be distended simultaneously using two cartridges. Acartridge (14) containing a flowable occlusive material (23) is thenconnected to the delivery catheter fitting (1), and the plunger (18) ispressed into the barrel (17) of the cartridge to deliver the flowableocclusive material (23) into and through the catheter, and exitingthrough the delivery end of the catheter (7) toward the target locationfor example, where it cures in situ. As depicted in FIG. 2B, occlusivematerial has been dispensed in the target area and has begun to cure insitu, forming an occlusion (25).

FIG. 2C shows the device at completion of the procedure. Once theflowable occlusive composition has reached the appropriate stage ofcuring, from beginning to cure to substantially curing into an occlusion(25), the operator uses the distension medium cartridge to deflate eachballoon, withdrawing the distension medium into the cartridge. Eachcatheter is retracted until it is housed within the introducer shaft (3)or, as shown in FIG. 2C, fully removed from the introducer. Ifnecessary, the delivery device stabilizer (4) is disengaged. Thedelivery device is then withdrawn from the patient, leaving theocclusion in place.

While the exemplary method shown in FIGS. 2A-2C follows a sequence inwhich both balloons are inflated, occlusive material is deliveredthrough both catheters, both balloons are deflated, and the catheterswithdrawn, a procedure in which all actions are completed initially byone delivery catheter followed sequentially by completion of all actionsfor the second delivery catheter is equally contemplated by the presentinvention and can be at the discretion of the operator. Further, itshould be understood that the exemplary method may comprise, as depictedin FIG. 2B, the sequential dispensing of occlusive material (23) fromeach of two delivery catheters placed in the uterine cornua (24), oralternatively simultaneous dispensing of occlusive material (23) throughboth delivery catheters.

The delivery system may comprise case of use features as depicted inFIGS. 3A-3C, which show further exemplary embodiments of a deliverysystem. FIG. 3A shows an external view of a delivery device with thedelivery catheters extended, wherein the delivery device comprises thefollowing components: an atraumatic tip (1) of the introducer shaft; endstructure (8) which is a balloon in the figure and, which is depicted inthe drawing as being inflated; the delivery end (7) of the deliverycatheter; the shaft of the introducer (3) comprising two introducershaft lumen exit ports (2). The introducer shaft lumen traverses theinterior length of the shaft and has openings for insertion of acatheter into the shaft and for the catheter to exit the shaft; thatcontain the delivery catheters and guide them into position; a deliverydevice stabilizer (4) to aid in correct placement throughout theprocedure; a housing (5) which is shown as an ergonomically designedhandle; a slide grip (26) that is used by the operator to move thedelivery catheters into position, wherein the grip has both up and downmovement for extension or retraction and side to side movement forrotation of the catheter tip and wherein the position of the grip can belocked in place to prevent further motion of the catheter once thedesired placement has been achieved; the shaft of the dual lumendelivery catheter (27); a occlusive material ampule (28) containing aflowable occlusive composition (23); and, a delivery plunger (29).

FIG. 3B shows an enlargement of the delivery device, as it would appearwhen it is proximal to the target site for delivery, where the numberedcomponents are as described for FIG. 3A.

FIG. 3C shows internal and optional aspects of the delivery devicedescribed in FIG. 3A, comprising the introducer shaft (3), wherein theintroducer shaft has two dual lumen delivery catheters (27) disposedwithin the introducer shaft lumen; a distal bifurcation housing (30),wherein each dual lumen catheter is directed by the distal bifurcationhousing (30) to one of two slide grips (26), allowing for individualmanipulation of each catheter by the operator; each catheter shaftcontinues from the slide grip (26) generally towards the deliveryplunger (29) wherein the two catheter shafts are each attached to theocclusive material bifurcation housing (31) having a channel whichdirects the flowable occlusive material (23) into each of the twodelivery catheters; and a component (32) capable of piercing theocclusion material ampule (28) when the plunger (29) is depressed toinitiate entry of the material into the delivery catheters. AlthoughFIGS. 3A-3C do not show a mechanism for inflation and deflation of theballoon, it should be understood that the delivery system may includesuch a mechanism. An embodiment of such a balloon inflation mechanism isdescribed in the present invention, although other embodiments of thismechanism could be used therein. A method of use for this embodiment ofthe delivery system may be like that of the delivery system depicted inFIGS. 1A-1C, or claimed herein. For example, the system comprisesintroducing the delivery device transcervically with the deliverycatheters contained within the introducer, each delivery catheter ismoved into position and the balloon inflated, the material is delivered,and the system withdrawn.

Depicted in FIG. 4 are further exemplary embodiments of the deliverydevice stabilizer (4), serving a similar or additional function to thatshown in FIG. 1, which allows for the fixation of the delivery system tothe cervix or hold the delivery device in position during use of thedelivery system of the present invention. These stabilizers may be usedas a component of the delivery device described herein or may be usefulfor holding in position any transcervical device or instrument having ashaft, including, for example, hysteroscopes and uterine cannulas.

FIGS. 4A-4C show a method of use of one embodiment of a delivery devicestabilizer which is slidable on the introducer shaft.

FIG. 4A depicts an example of a delivery device stabilizer (4) that fitsinto the cervical canal and expands to lock in place. Once theatraumatic tip (1) is in position at the uterine fundus (19), a deliverydevice stabilizer can be employed. As shown, the cervical canal (33) hasa larger inner diameter than the introducer shaft (3), which allowsmovement of the shaft when inserted. The cervix (20) has a large enoughopening to allow passage of the delivery device stabilizer (4) into thecervical canal in a collapsed or deflated state. As shown in FIG. 4B,the delivery device stabilizer (4) is moved transcervically into thecanal while the introducer shaft (3) is held in place, with theatraumatic tip (1) of the introducer shaft positioned at the top of theuterine fundus (19). The collapsed expandable portion of delivery devicestabilizer (4) is positioned within the cervical canal while a widerbase, of sufficient size to prohibit entry into the cervix, ispositioned against the external os. FIG. 4C shows the delivery devicestabilizer (4) in the uterine canal, wherein the expandable portion ofthe delivery device stabilizer (4) is expanded or inflated. Whenexpanded, the expansion portion of delivery device stabilizer (4) holdsthe delivery device stabilizer in place and prevents excessive motion ofthe introducer shaft (3). Although the delivery device stabilizer isshown in FIGS. 4B and 4C residing within the cervical canal, the designof this locking mechanism may also be envisioned to lie up to and eventhrough the internal os with any portion of the length designed forexpansion to enhance fixation.

FIG. 41) shows in detail an exemplary embodiment of the delivery devicestabilizer (4) with an expandable portion, wherein the delivery devicestabilizer mechanism may slide on the introducer shaft. The stop has ahollow core (36), which allows it to be mounted on the shaft of theintroducer where it is designed to slide for proper positioning. Anexpandable portion (34) is mounted on a non-expandable portion (37),which is attached to a base portion (35) that is of sufficient size toprohibit passage into the cervix. The expandable portion (34) may be aballoon that is expanded with a distension medium of one or more gasesor fluids, solid or semi-solid materials, to hold it in place. Theexpandable portion (34) may also be a mechanical device such as spiralor straight wire members that are mechanically actuated to effectexpansion. The expandable portion (34) may be expanded after insertionor may be inserted in a partially or fully expanded state prior toinsertion and further expanded as required after insertion into thecervix. Any elements for providing an expandable portion that are knownto those skilled in the art is contemplated by the present invention.

FIG. 4E illustrates an exemplary embodiment of a delivery devicestabilizer with a pre-formed internal portion. The delivery devicestabilizer comprises a hollow core (36) for attachment to and slidablemovement relative to the introducer shaft. The stabilizer comprises aportion that fits into the cervix (38) and a base portion that remainsoutside the cervix (35), wherein the portion that fits inside the cervixis shaped such that it locks or wedges into or through the cervicalcanal and limits motion. The shape may be rounded, wedge-shaped, or haveany other geometry that allows a snug fit within the cervical canal. Theportion that fits inside the cervix (38) may be made from a differentmaterial than the outer portion (35) or may be made from a combinationof materials. While rigid materials may be used, materials that arepliable, compressible, or expand in place such as by swelling, or somecombination thereof may be preferred. The delivery device stabilizermechanism may be designed and material selected such that the deliverydevice stabilizer mechanism collapses or is compressed while beingpushed through the cervix and then re-expands upon placement in thetarget location.

FIG. 4F shows an exemplary embodiment of a delivery device stabilizermechanism with a hollow core (36) to fit over a shaft that has a portion(38) that fits into or through the cervical canal as well as a baseportion (35) that has a cup shape that conforms to the outer geometry ofthe cervix. FIG. 4G illustrates placement of the exemplary deliverydevice stabilizer mechanism of FIG. 4F, showing that the base portionwith a cup shape conforms to the outer curvature of the cervix while theinner portion (38) fits within the cervical canal. The shape of theinner portion (38) may be rounded, wedge-shaped, or have any othergeometry that allows a snug fit. The portion that fits inside the cervix(38) may be made from a different material than the outer portion (35)or may be made from a combination of materials. While rigid materialsmay be used, materials that are pliable, compressible, or expand inplace such as by swelling, or combinations of such characteristics maybe used. Either the internal portion (38) or the base portion (35) maybe used alone or in combination as necessary to ensure appropriatefixation, stability, or both. It may be considered that the exemplaryembodiments described in FIG. 4 incorporate the function of a depth stopor uterine length marker, as shown in FIG. 1, into the design of thedelivery device stabilizer (4).

FIGS. 5A and 5B show the placement of an exemplary embodiment of adelivery device stabilizer referred to as a cervical clamp. In oneaspect of the present invention, the cervical clamp may be used in thedelivery system that does not incorporate an additional delivery devicestabilizer. In a further aspect of the present invention, the cervicalclamp may be used in a delivery system that also uses one or moreadditional delivery device stabilizers, which may include a depth stopor uterine length marker. FIGS. 5A and 5B show a cervical clamp (39)mounted on an introducer shaft (3), which is attached to a housing (5).The introducer shaft (3) is positioned such that the tip of the shaft(I) is positioned at the uterine fundus (19). As shown in FIGS. 5A and5B, the cervical clamp is used in combination with a delivery devicestabilizer (4) incorporating a depth stop function that marks andmaintains the insertion position of the atraumatic tip (1). The cervicalclamp (39) is introduced into the vagina (40) in a closed or foldedstate, as depicted in FIG. 5A. The clamp (39) is advanced over theintroducer shaft (3) until the leading edge nears the cervix (20), atwhich point, it is deployed and attached to the cervix (20), as depictedin FIG. 5B. The cervical clamp (39) attached to the cervix (20)functions to stabilize the introducer shaft.

FIG. 5C depicts an exemplary embodiment of a cervical clamp in which thegrasping arms (42) may remain in a folded state until acted upon by aforce. The cervical clamp, with a hollow core (36) to allow the clamp tomove over a shaft, includes grasping arms (42), which are actuated toattach to the cervix. In this embodiment, three grasping arms aredepicted. Other embodiments include devices with two, four, five, ormore grasping arms. The grasping arms are positioned such that the tipsof the arms (41) are in close proximity to the introducer shaft on whichthe cervical clamp is mounted. As depicted in FIG. 5C, tabs (43) areprovided that, when squeezed by the operator of the device, cause thearms (42) and tips (41) to move outward, causing the cervical clamp toopen. The clamp (39) is positioned over the cervix (20), and the tabs(43) are released, causing the clamp to fasten or attach to the cervix.The clamp is released by pressing on the tabs (43) to move the arms (42)outward, disengaging the tips (41) from the cervix. A further embodimentof the device may include a mechanism for movement of the clamp (39)relative to the shaft (3) and a mechanism for controlling the movementarms (42), wherein such mechanisms may be incorporated into the housing(5) of the delivery device.

FIG. 5D depicts a further embodiment of a cervical clamp in which thegrasping arms (42) may remain in an open state until acted upon by aforce. In this embodiment, four grasping arms are depicted. Otherembodiments include devices with two, three, five, or more graspingarms. A compression member (44), with a hollow core (36), slidesrelative to the shaft of the clamp (45) and imparts a compressive forceon the arms (42), deforming or moving them into a closed or foldedposition. To attach this embodiment to the cervix (20), the compressionmember (44) is advanced to compress the arms (42) to a folded state asdepicted in FIG. 5A. When the clamp (39) is in place near the cervix(20), the compression member (44) is retracted to allow the arms toopen. Subsequent advancement of the compression member (44) closes thearms (42) of the clamp (39), by deforming or moving the arms (42) tobring the tips (41) in to contact with the cervix (19). The compressionmember (44) may be advanced or retracted by mechanical means such asthreads, ratchet, slider, or other mechanisms. A further embodiment ofthe device may include a mechanism for movement of the clamp (39)relative to the shaft (3) and a mechanism for controlling the movementof the compression member (44) incorporated into the housing (5) of thedelivery system.

The tips of the arms (41) of the cervical clamp (39) may furthercomprise one or more grasping teeth, or may include other shapes ormechanisms for firmer or more comfortable attachment to the cervix (20).The tips (41) and arms (43) may be made from the same material or ofdistinct materials as required; for example, the tips may incorporate amaterial that is compressible and conformable to the cervix and may bedesigned to alter shape when in contact with the cervix to provideincreased comfort or improved gripping. One aspect of the inventionenvisions that the tips (41) interact with the cervix (20) in such amanner that the grip strength of the clamp is sufficiently low that thepatient feels little or no pain with minimal or no anesthesia whilehaving sufficient grip strength to hold, fix, and/or stabilize theposition of the introducer. The cervical clamp (39) has a cylindricallumen (36), which allows for mounting onto or sliding over theintroducer shaft (3).

FIGS. 6A-6E illustrate exemplary embodiments of conduit occlusionopening or re-opening devices, or reversal devices and methods,particularly for opening or re-opening one or more occluded fallopiantubes. The example discussed herein is directed to opening occludedfallopian tubes, but this description is in no way to be seen aslimiting the methods of the present invention. An introducer shaft (3)with one or more lumens may be used to deliver one or more catheters (9)to the area of the fallopian tube occlusion (25). Materials or devicesfor opening of occlusions or reversal of occlusions may be deliveredthrough or mounted on the delivery catheters (9). Occluded fallopiantubes may be treated simultaneously or sequentially. The delivery deviceallows for the opening or re-opening of one or more conduits without theneed for removal and re-introduction or substantial repositioning of thedevice. One or more reversal methods may be used in combination toeffect re-opening of the occluded conduit. It should be understood that,while depicted for use in re-opening occlusion in fallopian tubes, themethods and devices described herein may be useful for re-openingocclusions in any occluded, body conduit. As used herein, the termsopening and re-opening both refer to making a non-functional conduitfunctional again by providing an opening through or removing anocclusion.

FIG. 6A depicts the introduction of an enzymatic, solvent, or otherocclusion-degrading solution (46) to the site of the occlusion (25),such that the solution (46) degrades and removes the occlusion (25). Anintroducer shaft (3) is placed in position and delivery catheters (9)are advanced through the shaft through introducer shaft lumens to theexit port (2). The shaft lumen traverses the interior length of theshaft and has openings for insertion of a catheter into the shaft andfor the catheter to exit the shaft such that the catheters reach theocclusion (25). End structures (8), which may include a balloon, may beengaged, such as inflated, to limit delivery of the degrading solutionto the area of occlusion (25), and may prevent or minimize retrogradeflow into the uterus.

FIG. 6B shows a method of reversing an occlusion by passing a guide wireor small catheter (47) through the occlusion (25), thereby clearing theblocked fallopian tube. An introducer shaft (3) is placed in position,and one or more delivery catheters (9) are placed through the shaftthrough the introducer shaft lumens and out the exit port (2). The shaftlumen traverses the interior length of the shaft and has openings forinsertion of a catheter into the shaft and for the catheter to exit theshaft such that the catheters reach the occlusion (25) in one or both ofthe fallopian tubes. A guide wire (47) or a small catheter (47) ispassed through the delivery catheter (9) and advanced across or throughthe occlusion (25). The occlusion is removed or cannulated, therebyreopening the fallopian tube. Material for use in the small catheter maybe sufficiently stiff to allow for movement across and/or through theocclusive material or tissue. The small catheter may be further used toeffect delivery of a stent or other structure that maintains there-opened channel after reversal of the occlusion.

As depicted in FIG. 6C, one or more catheters (9) with attached balloon(48) may be placed through an introducer shaft (3) through theintroducer shaft lumens and out the exit port (2). The shaft lumentraverses the interior length of the shaft and has openings forinsertion of a catheter into the shaft and for the catheter to exit theshaft such that the catheters can be advanced such that the balloon (48)is within the area of occlusion (25). Inflation of the balloon mayeffect clearing or disruption of the occlusion. The catheter withattached balloon may pass directly through the introducer shaft (3) toreach the occlusion (25) or may pass through a larger catheter (notdepicted) that passes through the introducer shaft (3) to the area ofthe occlusion (25). The balloon may be used to effect delivery of astent or other structure that maintains the re-opened channel afterreversal of the occlusion.

FIG. 6D depicts a method of clearing fallopian tube occlusions by usinga cutting or debriding mechanism. The cutting mechanism (49) maycomprise or be similar to, for example, a device for atherectomy(directional coronary atherectomy), rotoblation (percutaneoustransluminal rotational atherectomy), or a cutting balloon. One or moredelivery catheters (9) are passed through an introducer shaft (3)through the introducer shaft lumens and out the exit port (2). The shaftlumen traverses the interior length of the shaft and has openings forinsertion of a catheter into the shaft and for the catheter to exit theshaft such that the catheters can be advanced to the vicinity of theoccluded region (25). A cutting device (49) is advanced through thedelivery catheter (9) to the occluded region (25). The cutting device isused to remove the occlusion (25), thereby reopening the fallopian tube.The cutting device may be used to effect delivery of a stent or otherstructure that maintains the re-opened channel after reversal of theocclusion.

FIG. 6E depicts a method of clearing an occlusion by using anenergy-producing device (50). Ultrasound, RF energy, microwave, laser,radiation, heat, or other energy sources may be used. An introducershaft (3) is placed, and one or more delivery catheters (9) are insertedthrough the introducer shaft through the introducer shaft lumens and outthe exit port (2). The shaft lumen traverses the interior length of theshaft and has openings for insertion of a catheter into the shaft andfor the catheter to exit the shaft so that the catheters can be providedto the area of the occlusion (25). An energy-producing device (50)mounted on a catheter or wire is passed through the introducing catheter(9) and into the occluded region (25). The occluded region is subjectedto energy from the energy source, which removes or disrupts theocclusive material and clears the occlusion. The catheter encompassingan energy producing device may be used to effect delivery of a stent orother structure that maintains the re-opened channel after reversal ofthe occlusion.

FIG. 6F depicts a uterus that has been subjected to one or more of themethods depicted in FIGS. 6A, 6B, 6C, 6D, and 6E. After treatment, theocclusion has been re-opened or removed, leaving patent fallopian tubes(51).

FIG. 7, an exemplary embodiment of a delivery device having one exitport, comprises the following subcomponents: the introducer tip (1)which is shaped for atraumatic insertion through the cervix to theuterine fundus; the introducer shaft (3), generally a structure whichmay be cylindrical or ellipsoidal in nature, which contains at least oneor more introducer shaft lumens ending in an exit port (2), the lumenstraverse the interior length of the shaft and have openings forinsertion of a catheter into the shaft and for the catheter to exit theshaft; a delivery device stabilizer (4) which in this example indicatesthe position of the tip relative to the point of entry, which may bemeasured based on markings along the shaft and which may further serveto hold the introducer in position; a housing (5) which may function asa handle and have an ergonomic design for gripping by the operator; andat least one catheter insertion hole (6) through which the deliverycatheters can be inserted into the introducer and guided through theintroducer shaft lumens to the exit port (2). The delivery devicestabilizer (4) shown in this example is a depth stop or uterine lengthmarker.

Now referring to FIGS. 8A-8E, wherein a schematic is shown of anexemplary embodiment of a method for deploying and using the exemplarydelivery system shown in FIG. 7 to effect an occlusion in fallopiantubes of a mammal or reopening of an occlusion. It should be understoodthat not all steps need be performed in every deployment of the deliverydevice. Further, it should be understood that additional steps may beadded as determined by one skilled in the art as necessary to increaseperformance, efficacy, or comfort of the patient undergoing the methoddepicted in FIG. 8.

In FIG. 8A, an operator holds the introducer housing (5) and inserts theshaft of the introducer (3) through the cervix (20) until the atraumatictip (1) contacts the uterine fundus (19) as determined by tactile feel,visualization such as ultrasound, or a combination of both tactile feeland visualization. When the atraumatic tip (1) is appropriately placedsuch as against the uterine fundus, the introducer shaft lumen exit port(2) is located such that the opening is directed toward the uterinecornua (24). Following contact of the atraumatic tip (I) with theuterine fundus (19), the delivery device stabilizer (4) is moved intoposition. In one embodiment, the delivery device stabilizer (4) maycomprise components or structures that function to ensure that theoperator maintains a fixed position of the introducer shaft, for examplefor preventing uterine perforation, as well as maintaining the positionof the shaft lumen exit port (2) during the procedure. In anotherembodiment, the delivery device stabilizer (4) may comprise componentsor structures to provide a depth stop mechanism or uterine length markerto the delivery device. In still another embodiment, the delivery devicestabilizer comprises components or structures to provide a depth stopmechanism or uterine length marker and stabilization to the deliverydevice. Exemplary stabilizers are seen in the figures.

FIG. 8B depicts the use of the delivery system for the introduction ofan occlusive material or re-opening material. With the introducer inposition, the operator moves a catheter, such as a double-lumen catheterthrough a catheter insertion hole (6) through the introducer shaft lumenuntil the catheter exits the introducer shaft lumen exit port (2), andthe delivery end (7) of the catheter is located at or within the uterinecornua (24) as determined by the operator's tactile feel, imaging suchas ultrasound, or a combination of feel and imaging. An exemplaryembodiment of a double lumen catheter is described in FIG. 1B, thoughany type catheter that will function in the methods and devices of thepresent invention is contemplated by the present invention.

Once the delivery end (7) of the catheter is positioned within theuterine cornua (24), the catheter position may be maintained by alocking mechanism which may be attached to the housing at or near thecatheter insertion hole (6), at another location within the housing, orby a mechanism that is separate from the housing and which serves tograb, clamp, hold or otherwise stabilize the catheter such that it doesnot move and such that the delivery end remains in the target location.In another aspect of the invention, an end structure of the catheter maybe used, for example by inflation of the balloon as described below issufficient to maintain position of the catheter, and no additionallocking mechanism may be required, or a balloon or end structure may beused with one of the catheter stabilizing components. For example, if aballoon catheter is used, a cartridge containing balloon distensionmedium (22), which has been previously prepared or mixed if such mixingis necessary, is then fitted to a fitting with a stopcock (12), thestopcock is opened, and the distension medium (22) delivered to effectinflation of the balloon or cartridge incorporated in the introducerhousing element is activated. Distension medium may comprise anyflowable or liquid material suitable for inflation of the balloon, suchmaterial being chemically compatible with the material of the balloonand may be biologically compatible in the event distension medium isintroduced into the uterine cavity or fallopian tubes. Exemplarydistension media include, but are not limited to, air and sterileisotonic saline solution.

Following inflation of the balloon, the stopcock is then closed, thecartridge disconnected from the fitting (12) or is automatically heldinflated by mechanism in the introducer housing. A cartridge containinga flowable occlusive material (23) is then connected to a catheterfitting, and the plunger is pressed into the barrel of the cartridge,either located outside or inside the introducer housing, to deliver theflowable occlusive material (23) into and through the catheter, andexiting through the delivery end of the catheter (7) toward the targetlocation, for example, where it cures in situ. As depicted in FIG. 8B,occlusive material has been dispensed in the target area and has begunto cure in situ, to form an occlusion (25) as shown in FIG. 8C.

FIG. 8C shows a device at completion of the procedure for occluding onefallopian tube, and rotation of the device so that the exit port (2) isdirected toward the untreated uterine cornua. Once the flowableocclusive composition has reached the appropriate stage of curing, frombeginning to cure to substantially curing into an occlusion (25), theoperator uses the distension medium cartridge to deflate the balloon,withdrawing the distension medium into the cartridge or a mechanismwithin the introducer housing can be triggered to automatically deflateor deflate upon activation. Balloon deflation may occur immediately orat some time after delivery of the occlusive composition. The cathetermay be retracted until it is housed within the introducer shaft (3) or,may be fully removed from the introducer and optionally, a new catheteris provided for the occlusion of a second fallopian tube. The introduceris not moved, nor is the delivery device stabilizer (4), but theintroducer shaft is rotated 180 degrees by rotation of the housing (5)so that the exit port (2) is directed toward the untreated uterinecornua.

As shown in FIG. 8D, a catheter is provided through the lumen of theshaft of the introducer and out the exit port (2) to be placed in theuterine cornua as described above. The distension medium (22) isprovided to a balloon located at the delivery end (7) of the catheter toinflate it. Occluding medium (23) is provided from an attached cartridgeor alternatively, incorporated within the introducer housing, throughthe catheter and out into at least the uterine cornua. FIG. 8E shows theplacement of two occlusions (25) in the location of the uterine cornuaand the initial retraction of the delivery device. The catheter has beenwithdrawn into the shaft of the introducer and the delivery devicestabilizer (4), if present, can be released or moved so that theintroducer tip (1) is retracted from the uterine fundus (19). Thedelivery device may then be removed from the patient, leaving theocclusion in place.

A single exit port device and methods, such as that shown in FIGS. 7 and8, may be used for removal of occlusions using elements and methodsdisclosed herein.

FIG. 9a shows two delivery catheters adjoined together for thesimultaneous advancement through a single lumen introducer to deliverocclusive material to each fallopian tube. The adjoined catheterscomprise the delivery ends (7 a/b) of each catheter through which theocclusive material is delivered to the target site; an end structure (8a/b) which is shown as a balloon, which may function to hold thecatheters in position and may prevent or minimize leakage of theocclusive material, away from the target; the shafts of the catheters(36 a/b) which for a certain length are fused together and are separateddistally (37 a/b) to allow independent movement to each cornua. In thisfigure, each catheter is shown with a pre-formed curve, in the area thatis not fused, which functions in movement of the delivery end of thecatheter from the introducer shaft into the cornual aspect of theuterus. Each catheter may include two lumens, one for inflation of aballoon and one for delivery of the occlusive material. The catheterlumen may be bifurcated so as to provide attachments to two fittings (38a/b) that each mates with a cartridge that contains flowable material tobe delivered, such as the occlusive material; and two fittings with astopcock (35 a/b) that mates with a cartridge that contains material tobe delivered, such as distension media for inflation and deflation ofthe balloon. One aspect of the present invention comprises a deliverycatheter that is a double lumen delivery catheter. It should beunderstood that the delivery catheter may comprise a number of featuresand designs known in the art for catheters and that would be useful forthe function of the delivery system. The catheters of the presentinvention may be single lumen or dual lumen catheters, or othercatheters that would function in the present invention. One aspect ofthe invention comprises a stopcock is used to prevent leakage of theballoon distension medium after placement. It should be understood thatother devices, such as a valve or diaphragm, including a self-scalingdiaphragm, may also serve the same function and be useful in obtainingand maintaining inflation of the balloon of the present invention. Thecatheters may have end structures other than balloons and theseembodiments would not require the elements needed for ballooninflation/deflation. End structures may comprise single or double walledballoons, cups, discs or other structures known to those skilled in theart.

FIG. 9B1-6 shows embodiments of cross section views of the introducershaft lumen, which may be a single one lumen (1), dual lumen with aseptum horizontally across the shaft (2), dual lumen with the septumvertically across the shaft (3), dual lumen with individual rounddiameter channels (4), dual lumen with individual oval or similar shapeddiameters (5) and dual lumen with a free forming septum (6). The shapeof the lumens is intended to enhance advancement of one or morecatheters through the shaft. The septum construction dividing the lumencan be solid, rigid, semi-rigid or flexible, made from a material of anyof a variety of durometers, or made of the introducer shaft material ordifferent material bonded, fused or joined to the introducer shaftmaterial. The septum traverses the length of the lumen of the introducershaft, from the housing to an area below or proximal of the exit port(s)or substantially near the exit port(s).

The delivery systems of the present invention comprise elements forintroducing delivery devices into the body, elements for providingocclusive material such as reservoirs and pumps, devices for in situdelivery of compositions comprising occlusive materials, elements forpolymerizing or coagulating the occlusive materials, including usingmechanical, biological or chemical methods, elements for visualizationof procedures, pre- and post-procedural compositions and methods oftreatment, elements and compositions for supporting or inducing tissueingrowth or wound healing or similar type response or degradation of theocclusive material, and elements for re-opening of the occluded conduit.

The present invention further comprises methods for occluding fallopiantubes that are useful for providing female sterilization. It is wellknown in the art that a primary cause of naturally occurring infertilityin females is blockage of the oviducts from the ovary to the uterus.Females having this natural condition normally do not even realize itexists and do not suffer any adverse side effects besides beinginfertile. Moreover, the condition can sometimes be successfullyreversed, thus restoring the ability to bear children. Based upon theobservations of naturally occurring oviductal occlusion, the creation oftubal occlusions by external intervention has arisen as a potentialmeans of effecting female sterilization.

Aspects of the present invention comprise a delivery system,compositions comprising one or more occlusive materials, and a methodfor tubal occlusion and more particularly occlusion of the fallopiantubes of a female mammal for the purpose of sterilization, which may bereversible at a later time. In one aspect of the invention, a deliverydevice is inserted and positioned so as to reach the area in which theocclusion is desired while the operator either tactilely determines theplacement and/or visualizes utilizing imaging the delivery device toensure correct placement. Once in place, the operator instills theocclusive agent through a lumen in the delivery catheter, creating theocclusion. The delivery device is then withdrawn, leaving the occlusionin place. Confirmation of occlusive material placement may be madeutilizing visualization, such as ultrasound. Fibrous tissue grows intothe material or a wound healing response is elicited as the occludingmaterial resorbs or degrades, leaving an occlusion fashioned of thepatient's own tissue or an obliterated lumen. The delivery system may beused to deliver an agent, such as a device or composition, to reversethe occlusion, and methods for re-opening the occlusion are described.

An aspect of the present invention comprises a delivery system anddevice comprising a transcervical introducer sheath comprising a housingand a shaft, parts of which may be made of a standard medical-grademetal or plastic such as stainless steel, nylon, PTFE, polyurethane,FEP, pebax, or HDPE, which may be naturally sonolucent or may requireenhancement of ultrasound visibility by coating with a sonolucentmaterial or otherwise modifying the material. The sheath may comprise anatraumatic tip to allow for comfortable placement and, combined withselection of a suitably flexible material, to prevent damage to theuterine wall. The introducer shaft has sufficient diameter to allow forintroduction of other components of the delivery system. The introducermay contain one, two or more lumens that guide catheters into position,for example delivery catheters for delivery of occlusive materials. Theintroducer may include a mechanism to modify the angle of the introducerrelative to the surrounding tissues, such as the cervix or uterus, toallow for a better fit to the anatomy of the individual patient,including such individual variations as ante- or retroverted/ante- orretroflexed uterus. Modified versions of the introducer may allow foruses other than for the occlusion of the fallopian tube(s), such as thelocalized delivery of contrast media for confirmation of tubal patencyor the delivery to or removal from the fallopian tube(s) of othermaterial or devices for diagnosis, treatment, or examination of thetube, including the delivery of systems for re-opening an occlusion. Oneaspect, of the introducer sheath is that it can be visualized usingimaging techniques such as ultrasound. Visualization may be used toguide accurate placement and to ensure that the tip of the device doesnot penetrate the uterine wall. Operator feel may be used to guideaccurate placement and to ensure that the tip of the device does notpenetrate the uterine wall. A delivery device stabilizer may be includedto ensure that accurate placement is maintained throughout theprocedure. The delivery device stabilizer may comprise or include anelement to fix or hold the introducer in place, such as a mechanism ordevice to attach or hold the introducer within the cervix or tootherwise maintain the device in the desired position, minimizing riskto the patient and allowing the operator greater flexibility to carryout other aspects of the procedure. Fixation may be accomplished throughphysical elements such as clamping, suction, wedging, inflation, or byother elements that maintain the device in the desired position.

A delivery system of the present invention comprises a device that canbe configured in a collapsed, retracted, or folded form for insertionthrough the cervix, which may comprise an introducer sheath. Afterintroduction, the device is positioned so that an atraumatic tipcontaining a single or multiple holes or exit ports at the tip of thedevice to be positioned near the desired location so that a catheter mayreach the desired location, such as within the cornual aspect of theuterus at or near the ostium of a fallopian tube. The one or more exitports allow for a catheter exiting the port to be in an orientation inthree dimensional space that is convenient and beneficial for providinga material or for performing an activity at a desired location. Oneaspect of the catheter is that it can be visualized using imagingtechniques such as ultrasound. Visualization may be used to guideaccurate placement of the catheter and to ensure that the tip of thecatheter does not penetrate the uterine wall. Operator feel may be usedto guide accurate placement of the catheter and to ensure that the tipof the catheter does not penetrate the uterine wall.

The present invention comprises methods for providing a delivery devicethat has at least one end of a delivery catheter with an opening that isplaced within the cornual aspect of the uterus at or near the ostium ofa fallopian tube. In one embodiment, the delivery device comprises twodelivery catheters, with each catheter having its delivery openingpositioned simultaneously or sequentially at the ostia of both fallopiantubes. In an embodiment of the present invention, a method comprisesproviding a delivery device which comprises one delivery catheter, witha catheter having its delivery opening positioned at the ostia of afallopian tube. In other embodiments, such a device may be shaped like aY, a T, or an arrow wherein one or more exit ports are positioned nearor within the uterine cornua or at or near the ostia. The deliverysystem may utilize existing catheter-based technology, for example, oneor more balloon catheters, and may incorporate standard materials suchas Pebax, nylon, PTFE, polyurethane, vinyl, polyethylene, ionomer,polyamide, polyethylene terephthalate, and other materials. Thesematerials may be naturally sonolucent or may be modified to enhancetheir ultrasound visibility, such as by coating or the inclusion of airbubbles within the material. Embodiments of the present invention mayinclude an element for controlled flexion or rotation of the deliverysystem, which may aid in positioning one or more ends at the desiredanatomic location. The catheters may be designed with one or more curvesthat ensure that the tip is guided to the uterine cornua. Such curvesmay be either pre-formed to suit a majority of female reproductiveanatomies or may be selected based on the individual anatomy of a singlefemale patient.

The present invention comprises methods for occlusion of fallopian tubescomprising delivery of devices, such that the methods incorporateoperator tactile feel and/or intra-procedure visualization withouthysteroscopy, and positioning of the delivery end of a delivery catheterat or within the uterine cornua at or near the ostia of both fallopiantubes without the need for removal and reintroduction ofinstrumentation. Embodiments of the present invention comprise deliverydevices that are sized appropriately for a general population ofpatients and also comprise delivery devices that are custom-fitted andindividually tailored to meet individual patient anatomical needs.Delivery devices taught in the prior art, such as U.S. Pat. Nos.5,746,769, 6,145,505, 6,176,240, 6,476,070, 6,538,026, 6,634,361,6,679,266, and 6,684,384, 5,954,715, 6,068,626, 6,309,384, 6,346,102,and 6,526,979 do not consider individual patient anatomy, may requirethe use of a hysteroscope for direct visualization, and necessitatecannulation of each tube sequentially, with the need to reposition,withdraw and reinsert the device, enhancing the technical difficulty ofthe procedure and consequently the inherent risk of failure.

One aspect of this invention contemplates the use of pre-procedureimaging, such as by ultrasound, to allow for selection or adjustment oflengths and angles of the deployed delivery device and selection ofappropriate delivery device stabilizer to accommodate individual patientanatomy. This pre-procedure imaging is used to rule out anomalies thatmay preclude use of the system and may be used to determine the uterinewidth between the fallopian tubes to select the correct size deliverysystem or to adjust the angle or shape of a delivery end so it may beproperly located within or at the uterine cornua or at or near theostium of a fallopian tube for deployment. Imaging may also elucidatethe size and shape of the cervical os and canal, guiding selection ofsize and shape of delivery device stabilizer or spacer. Alternatively,one of a set of predetermined sizes of the delivery system could beselected based on the pre-procedure imaging information. The ability toadjust placement of the catheter delivery ends or tips, including theangle and length for each individual end or in combination, during theprocedure based on tactile feedback, imaging, or both tactile andimaging information is also contemplated. Other pre-procedure methodsinclude the use of hormonal medications to control estrogen/progesteronecycle changes or prevent placement of the device during pregnancy, theuse of pre-operative medications such as anti-infective or immuneresponse therapies, and the use of nonsteroidal anti-inflammatory drugsto minimize discomfort and tubal spasm.

The present invention further comprises post-procedure methods andcompositions. Post-procedure methods may comprise, for example,ultrasound or X-ray visualization, to allow for confirmation that theocclusive material was delivered correctly or continues to provide anocclusion over time. Post-procedure methods and compositions may furthercomprise the use of hormonal agents to prohibit menstrual shedding ofthe endometrium and is also contemplated to minimize the risk ofexpulsion for a period of time, for example to allow for a period oftime for resorption, or degradation of the occlusive material and tissueingrowth or scarring, wound healing or similar type response. Forexample, use of a long-acting hormonal medication such as an injectablemedroxyprogesterone acetate depot may serve the function of both thepre- and post-operative hormonal therapy without the need for relianceon patient compliance. Post-operative methods and compositions mayfurther comprise antibiotic or steroidal compositions.

Methods of the present invention comprise visualization of one or moresteps of the methods. Visualization of the insertion, placement of thedevice, release of the occlusive composition, and confirmation ofocclusive composition location are included in methods for providing theocclusive material. Visualization of the occluded region, removal of theocclusive material, reopening of the conduit and testing for return offunctionality of the conduit are included in methods for reversing theocclusion of the conduit. Such visualization methods are known to thoseskilled in the art. U.S. Pat. Nos. 4,731,052 and 4,824,434 teach thatultrasound may be used for visualization of internal structures. Thecompositions and devices of the present invention comprise materialsthat allow for visualization, such as by ultrasound, during theprocedure to ensure appropriate patient selection and device placementand localization, and for post-application monitoring to confirmappropriate material placement and the presence of an occlusion.

Once the delivery device is appropriately placed, the occlusive materialis introduced through the delivery device to create the occlusion of thefallopian tubes. In one aspect of the invention, the delivery device hasindividual lumens in the shaft of the introducer, with one or more exitports to provide a catheter delivery end or tip directed toward theopening of a fallopian tube. An aspect of the invention allows for thesimultaneous or sequential delivery of occlusive material to thefallopian tubes without the need to withdraw and reinsert orsubstantially reposition the device. The occlusive material is deliveredby actions of the operator manually or automatically once the device isin position. One aspect of the invention contemplates that the occlusivematerial may be visualized by imaging such as ultrasound. Materials maybe naturally sonolucent or may be modified to have enhanced sonolucencyby the introduction of materials or bubbles such as microbubbles of airor other gases. These microbubbles may be present within the materialprior to attachment to the delivery system or may be introduced into thematerial during the delivery process, such as through the use of acavitation mechanism.

It is contemplated that the methods taught herein are effective with oneapplication of occlusive material to at least one conduit, though themethods comprise at least one application to at least one conduit.Embodiments also comprise one or more applications of occlusive materialto at least one conduit during one delivery cycle. For example, once thedelivery device is in place in the uterus, with at least one end of thedelivery catheter at the site or sites to be occluded, occlusivematerial may be applied once, and then, without removal, one or moreother applications of occlusive material may be performed.Alternatively, occlusive materials may be placed at the site or sitesfor occlusion over multiple treatments. For each treatment, the deliverydevice would be inserted and removed. Such multiple applications mayoccur on consecutive days of insertion and removal or the days ofinsertion and removal may be interspersed with days of no applicationsof occlusive material. Such treatment regimens may be designed withindividual patient needs taken into account by those skilled in the art,such as the treating physicians. Such treatment regimens may utilize thesame or different occlusive compositions at each application.

The occlusive compositions include natural or synthetic materials.Natural materials include those found in animals or plants and notnecessarily in the species in which they are used. Synthetic materialsinclude any materials that can be made by humans or machines inlaboratory or industrial settings. The compositions may comprisematerials that are initially mostly fluid that polymerize in situ tobecome solid or semi-solid materials, may comprise solid materials thatmay or may not change properties such as flexibility, once placed at thesite or sites for occlusion, may comprise a mixture of fluids with gas,solid articles or both, dispersed therein. The occlusive materialcompositions may be a pre-formed shaped material that is released by thedevice once one or more delivery ends are in position, and thecompositions may comprise occlusive material that starts as a liquid orsemi-solid that cures in situ. The compositions of the present inventionmay include solid structures such a stents, rods, pellets, heads, andother tissue bulking agents that provide a solid structure to theocclusion formed at the site or sites. Compositions of the presentinvention may also combine pre-formed structures, such as spheres orparticles, with material that starts as a liquid or semi-solid and curesin situ, entrapping the preformed structures.

One aspect of the present invention comprises an occluding compositioncomprising a liquid that is mixed prior to delivery or does not requirepre-mixing such as the single liquid composition, is ultrasound visible,and cures upon delivery into and through the tubal ostia within 3 cm ofthe ostium, within 5 cm of the ostium or within 8 cm of the ostium, toprovide mechanical blockage and is at least 75% resorbed at a range ofbetween about 30 to about 365 days. In one embodiment, the occludingcomposition is not hydrophilic and does not swell in the presence offluids in the environment. In another aspect, the occlusive compositionforming the occlusion may aid in the initiation or stimulation of tissuegrowth into the occluded site, wherein the occlusion is replaced bytissue that maintains the occlusion after resorption of the occlusionmaterial. In another aspect, the occlusive composition forming theocclusion may aid in the initiation of stimulation of a wound healing orsimilar type response at the occluded site, wherein the occlusionremoves an internal layer of the fallopian tube lumen, allowing forcomplete healing of the lumen walls, resulting in obliteration of thelumen. In another embodiment, the occluding composition is ultrasoundvisible once it has cured in situ. In another aspect, an embodiment ofthe invention contemplates use of an occlusive material that has afunctional lifespan wherein for a period of time it forms the physicalocclusion or blockage of the lumen, and after period of time, theocclusive material is gone, having been resorbed or degraded, but is notreplaced by tissue ingrowth or wound healing, so that the lumen is againopen and functional.

In a further aspect of the present invention, the occlusive materialcomprises a two component liquid comprising a resorbable polymersolution or solid polymer component and a liquid cyanoacrylate tissueadhesive component. The resorbable polymer may be a polyester polymerselected from polylactide, polyglycolide or polycaprolactone, or apolyester copolymer selected from poly(lactide/glycolide) acid (PLGA) orpoly(lactid-co-ε-caprolactone) (PLCL), or polyactylic (to includemethacrylates and cyanocylates), or polyvinylics including polyvinylalcohols, polyvinyl pyrrolidones, polyvinyl ethers, polycyanoacrylates,polyanhydrides, such as maleic anhydride groups. These polymers may becopolymers or blends of these. The resorbable polymer solution orpolymer solid may be any other known polymer or copolymer such as thosebased on a polyether backbone. The polymer solution may be anycomposition that undergoes degradation upon contact with body fluids aswould typically be encountered in such structures as the fallopian tubesor other comparable animal ducts. The polymer solution may be ofcopolymer or multi-polymer compositions. It may be of varying molecularweight depending upon the need of a particular viscosity. The polymersolution may also be composed of diluents or other additives to controlthe level of fluidity for ease of blending into the cyanoacrylatemonomer. The chosen polymer solution or solid polymer may be of anymaterial that has been found to be compatible with human or animaltissue or of such activity that will enhance the desired occluding ofthe treated passageway. The cyanoacrylate tissue adhesive componentcomprises any of a number of alkyl- or alkoxyalkyl-2-cyanoacrylates suchas methyl, ethyl, propyl, butyl, n-butyl-2-cyanoacrylate, methoxypropyl,methoxybutyl, 2-methoxybutyl-2-cyanoacrylate or any other suchcyanoacrylates either as a single monomer or combinations thereof. Thetechnical literature is abound with the numerous and typical suchmaterials of which any and all may be utilized as a component, either asa single monomer composition or as formulations curing into variouspolymer, co-, and multi-polymer occluding agents. Components may bemixed prior to entry in the catheters for delivery. In curing, thecyanoacrylate components polymerize and results in the desired occlusionin which the non-cyanoacrylate components are homogeneously orheterogeneously incorporated. The cyanoacrylate adheres to the lumenwall to anchor the occlusion in place. Non-cyanoacrylate components maybe included, and these components may encourage more rapid degradationof the occlusive composition.

A single liquid composition is also contemplated. The single liquidcomposition comprises a tissue adhesive, such as a cyanoacrylate with anano- or micro-particulate material, which may be organic or inorganicin composition. In one aspect of the invention, the particles arecapable of visualization by ultrasound. The particles and tissueadhesive are combined prior to delivery to the target site. In anotheraspect of this embodiment is the use of particles which can beformulated and remain suspended or can be reconstituted into suspensionso as to eliminate the on-site preparation. The composition cures by thepolymerization of the tissue adhesive, entrapping the particles, andanchors the occlusion in the lumen by adhesion to the lumen wall.

In a further aspect of the invention, a cyanoacrylate composition withpolar moieties, such as ether segments is contemplated as an occlusivematerial so that rapid loss of the occlusive material is achieved, from1 to 12 months, under 12 months, time post delivery, in the presence ofproteinaceous substances, principally animal or human tissue. The rapiddegrading or resorbing cyanoacrylate tissue adhesive component(s)comprises any of a number of cyanoacrylates, such as methoxyethyl,ethoxyethyl, and methoxypropyl cyanoacrylates, including knowncarbalkoxyalkyl 2-cyanoacrylates. The cyanoacrylate component can beused alone or in combination with other cyanoacrylate components and/orin combination with resorption-enhancing organic or inorganic materialsthat further accelerate expulsion from the patient. Such additivesprovide the freedom to fine tune the desired time to degrade, resorb oreliminate the occlusive composition from the patient. Such compositionsare noted in examples 9 and 10.

Another aspect of the present invention comprises a group of occludingsubstances that use a two part system similar to the foregoing liquidpolymer compositions. These substances are two part isocyanates/polyols,two part acrylic cures similar to the reactive and anaerobic adhesivesof the Loctite/Henkel Corporation and similar sources, or two part epoxysystems. The isocyanates undergo evolution of carbon dioxide and promoteporosity and rapid resorption or degradation. These compositions serveto exemplify the numerous possible candidates for creating theseocclusions. It must further be understood that these two part or, onsite prepared systems, can also be combined with other occludingcompositions. For example the carbon dioxide releasing, porosityinducing, nature of the isocyanate can be combined with the other tissueadhesives, such as the cyanoacrylates to provide the occlusive andresorbing or degrading compositions.

In a method of the present invention, the resorbable or degradableoccluding compositions and the location of the occlusion to a portion ofthe fallopian tube, for example, extending over at least 0.5 cm of theFallopian tube, provides for a persistent block and creates a permanentcontraceptive method. The resorbable or degradable nature of theoccluding composition and the proximity of the occlusion to the ostia,extending over a limited length of the fallopian tube, may allow forease in the reversibility of the contraceptive method. As the occlusiveimplanted composition is resorbed or degraded, there is ingrowth oftissue or a similar type response that maintains the occlusion. Thetissue occlusion so firmed can be recanalized to provide an open conduitfor fertilization without the need for surgical removal and reappositionof the tube across the area of the occlusion.

A wide variety of materials are known in the art that can be used toform the conduit occlusions of the present invention, such as oviductocclusions. U.S. Pat. No. Re 29,345 teaches the use of silastic that ispartially pre-formed and partially in situ cured. U.S. Pat. No.4,185,618 teaches the use of a gel-forming carrier substance that holdsin place a tissue fibrosis-promoting material. U.S. Pat. Nos. 4,365,621and 4,509,504 describe the use of a swelling material that is inert andpermanent. U.S. Pat. No. 6,096,052 describes the use of a mesh-basedmaterial that supports fibrous tissue ingrowth. U.S. Pat. No. 4,700,701describes the use of a resorbable plug in combination with physicaland/or chemical elements of inducing a scarring reaction. U.S. Pat. No.5,989,580 incorporates the use of a biocompatible, non-degradableimplanted polymer of several types that can be removed by dissolution.U.S. Pat. No. 6,605,294 teaches the use of absorbable polymers,pre-shaped with at least one rod-shaped portion, to occlude fallopiantubes. U.S. Pat. No. 5,894,022 teaches using a composition that may forma degradable mesh. U.S. Pat. Nos. 6,371,975, 6,458,147, and 6,743,248teach the use of a polyethylene glycol and protein composition for theocclusion of vascular access puncture sites. The present inventioncomprises these and other occlusive compositions fir blocking a conduitthat may be introduced using the delivery devices of the currentinvention.

One aspect of the occlusive compositions of the current inventioncomprises a resorbable or degradable material capable of providing aninitial mechanical blockage and initiating or supporting the tissueingrowth or wound healing or similar type response necessary to createthe occlusion and/or an adhesive composition that maintains the positionof the material during curing and the initial phase of tissue ingrowthor wound healing. U.S. Pat. Nos. 4,359,454, 6,476,070, and 6,538,026teach the use of cyanoacrylate, and in particular a compositioncontaining either n-methyl or n-hexyl cyanoacrylate, as a resorbable,yet scar-promoting, material. Other patents teach compositions ofpolymerizable monomers, such as cyanoacrylates, alone or in combinationwith other materials, such compositions that may be useful as occlusiveagents or adhesives in the present invention and/or as resorbablematerials capable of initiating or supporting tissue ingrowth to form apermanent adhesion. These include U.S. Pat. Nos. 5,328,687, 5,350,798,6,010,714, 6,143,352, 6,174,919, 6,299,631, 6,306,243, 6,433,096,6,455,064, 6,476,070, 6,538,026, 6,579,469, 6,605,667, 6,607,631,6,620,846, and 6,723,144.

A further aspect of the current invention includes occlusive materialsthat are delivered in a solid or non-solid form which may be used todeliver or adhere materials that may be useful in promoting or formingocclusions or which may be useful in forming occlusions in and ofthemselves whereas such material may be resorbable, degradable orpermanent. Such materials include dry compositions that hydrate and formcrosslinked hydrogels, as taught by U.S. Pat. No. 6,703,047. U.S. Pat.Nos. 5,612,052, 5,714,159, and 6,413,539 teach self-solvating polyestercopolymers that form hydrogels upon contact with body fluids. U.S. Pat.No. 4,804,691 teaches compositions of hydroxyl-terminated polyesterscrosslinked with diisocyanate. U.S. Pat. No. 6,723,781 teachescrosslinked, dehydrated hydrogels. Hyaluronic acid based hydrogels aretaught in U.S. Pat. Nos. 5,866,554 and 6,037,331. Two part hydrogels aretaught in U.S. Pat. No. 6,514,534. Crosslinked bioadhesive polymers aretaught in U.S. Pat. Nos. 6,297,337 and 6,514,535. Thermosensitivebiodegradable polymers are taught in U.S. Pat. No. 5,702,717.

The present invention comprises compositions that form an occlusion in aconduit, wherein the occluding material is resorbed or biodegraded bythe body in a range from at least about 20% to about 100%, or in a rangefrom at least about 20% to about 80%, from a range of at least about 20%and about 60%, from a range of at least about 30% to about 50%, from arange of at least about 30% to about 80%, from a range of about 70% toabout 100%, and from a range of about 40% to about 100%. Occludingmaterials may be resorbed or degraded 80% to 100% over a time period of1 to 90 days, 1 to 60 days, 1 to 45 days, 1 to 30 days, 5 to 25 days, 10to 20 days, 5 to 10 days, 1 to 10 days, 1 to 15 days, from 30 to 90days, from 15 to 30 days, from 20 to 30 days, from 10 to 30 days, from10 to 60 days, from 10 to 90 days, so that the occlusion remaining isformed by tissues of the patient or a wound healing response or similartype response. Such resorption or degradation may occur substantiallyover a period of time from about 30 days to 365 days, from about 30 daysto 180 days, from about 30 days to 90 days, from about 60 days to 365days, from 60 days to 180 days, or from about 90 days to 365 days. Acomposition comprises a material that is resorbed or biodegraded by thebody in a range of at least about 20% to substantially 100% in a periodof time of about 30 days to 365 days, where the initial occlusion formedby the material is maintained thereafter by the tissue that grows intothe site or wound healing response or similar type response.

The present invention comprises compositions that form an occlusion in aconduit, wherein the occluding material is not resorbed or biodegradedby the body but instead the compositions is expelled, such as infragments, over time, from the conduit. Fragments of the occludingmaterials may be expelled over a time period of 1 to 90 days, 1 to 60days, 1 to 45 days, 1 to 30 days, 5 to 25 days, 10 to 20 days, 5 to 10days, 1 to 10 days, 1 to 15 days 30 to 90 days, 15 to 30 days, 20 to 30days, 10 to 30 days, 10 to 60 days, 10 to 90 days, so that the occlusionremaining is formed by tissues of the patient or a wound healingresponse or similar type response. Such expulsion of occluding materialmay occur substantially over a period of time from about 30 days to 365days, from about 30 days to 180 days, from about 30 days to 90 days,from about 60 days to 365 days, from 60 days to 180 days, or from about90 days to 365 days. A composition comprises a material that is expelledby the body in a range of at least about 20% to substantially 100% in aperiod of time of about 30 days to 365 days, where the initial occlusionformed by the material is maintained thereafter by the tissue that growsinto the site or wound healing response or similar type response.

The present invention contemplates use of an in situ curable material,which lowers the risk of expulsion by allowing the material to conformand adhere to the walls of the conduit, or specifically the uterusand/or fallopian tube. Compositions capable of in situ curing preferablycomprise a material that is flowable at a temperature outside or withinphysiologic limits but curable at physiologic temperatures such as thosetaught by U.S. Pat. Nos. 5,469,867 and 5,826,584. High viscosity liquidscapable of delivering and maintaining materials in place that are usefulfor the present invention are taught in U.S. Pat. Nos. 5,747,058,5,968,542, and 6,413,536. Alternatively, the material may cure oncontact with the tissue environment as described in U.S. Pat. Nos.4,359,454, 6,476,070, and 6,538,026; on contact with a curing agent (astypified in two part systems) as described by U.S. Pat. Nos. 5,278,202and 5,340,849; or on dissipation of the solvent as described by U.S.Pat. Nos. 4,938,763, 5,278,201, 5,324,519, 5,487,897, 5,599,552,5,599,552, 5,632,727, 5,702,716, 5,728,201, 5,733,950, 5,736,152,5,739,176, 5,744,153, 5,759,563, 5,780,044, 5,792,469, 5,888,533,5,990,194, 6,120,789, 6,130,200, 6,395,293, 6,461,631, 6,528,080, and Re37,950 as well as world-wide patent numbers WO 97/42987, WO 99/47073,and WO 00/24374.

The present invention comprises use of compositions made from onematerial or a combination of more than one material to form theocclusion, particularly compositions that comprise materials that cureor polymerize by differing mechanisms or differing rates by the samemechanism. For example, the compositions may comprise a combination oftwo materials, one of which cures or polymerizes because an activatingagent is present and the other cures, polymerizes or solidifies, all ofwhich are interchangeable terms, because of the pH of the environment inwhich it is placed. Components of the mixture may serve different oroverlapping roles; for example, a tissue adhesive component mayprimarily serve to minimize expulsion of the implant while tissuein-growth or wound healing or similar type response is occurring, whileanother component may primarily initiate or support the tissue growth orwound healing or similar type response. In another example, a tissueadhesive component(s) may initially serve to solidify and hold theimplant at the desired location and begin the degradation process as thetissue ingrowth, wound healing, or similar type response is on-going.The tissue adhesive component may be selected from the group ofmaterials containing cyanoacrylates, polyacrylic acids, polyethyleneglycols, modified polyethylene glycols, thrombin, collagen,collagen-based adhesives, fibrin, fibrin glue compositions,gelatin-resorcinol-formaldehyde-glutaraldehye (GRFG) glue, autologousblood in combination with collagen and/or thrombin, crosslinked albuminadhesives, modified glycosaminoglycans,poly(N-isopropylacrylamide)-based adhesives, alginates, chitosan, andgelatin, crosslinked with carbodiimide or genepin, among others, in aproportion of the overall composition from about 5% to 50%, from about75 to 95%, from about 60%-80%, from about 5% to 25%, from about 10% to50%, or from about 10% to 25%. The material added primarily for theinitiation or support of tissue ingrowth or wound healing or similartype response may be chosen from the group consisting of solid orsolvated resorbable or degradable polymers, including the resorbable ordegradable polyesters or their copolymers. The occlusive promotingcomponent, including or excluding the presence of solvent, may comprisefrom about 1 to 15%, 20% to 80%, from about 50% to 80%, from about 40 to70%, or from about 50% to 90% of the overall composition.

Additional components may be included to stabilize the overall mixtureor to control the viscosity, curing time, resorption timeframe,plasticity, or to enhance visualization of the material. Such agents mayinclude: polymerization inhibitors and stabilizers including, forexample sulfonic acid, lactic acid, acetic acid, sulfur dioxide,lactone, boron trifluoride, hydroquinone, hydroquinone monomethyl ether,catechol, pyrogallol, benzoquinone, 2-hydroxybenzoquinone, p-methoxyphenol, t-butyl catechol, organic acid, butylated hydroxyl anisole,butylated hydroxyl toluene, t-butyl hydroquinone, alkyl sulfate, alkylsulfite, 3-sulfolene, alkylsulfone, alkyl sulfoxide, mercaptan, andalkyl sulfide; emulsifying agents such as polyvinyl alcohol; echogenicagents such as microbubbles of air or gas, microparticles or spheres ofcrosslinked albumin with entrapped air or gas (Albunex), sonicatedalbumin, gelatin-encapsulated air or gas bubbles, nanoparticles,microparticles, spheres, or microcapsules of resorbable materials withentrapped air or gas, particles of other materials with entrapped air orgas; contrast agents such as metal particles, metal nanoparticles, metaloxide nanoparticles; viscosity-modifying materials such as crosslinkedcyanoacrylate, polylactic acid, polyglycolic acid, lactic-glycolic acidcopolymers, polycaprolactone, lactic acid-caprolactone copolymers,poly-3-hydroxybutyric acid, polyorthoesters, polyalkyl acrylates,copolymers of alkylacrylate and vinyl acetate, polyalkyl methacrylates,and copolymers of alkyl methacrylates and mono-enes and or di-enes; andplasticizers such as dioctyl phthalate, dimethyl sebacate, trethylphosphate, tri(2-ethylhexy)phosphate, tri(p-cresyl)phosphate, glyceryltriacetate, glyceryl tributyrate, diethyl sebacate, dioctyl adipate,isopropyl myristate, butyl stearate, lauric acid, dibutyl phthalate,trioctyl trimellitate, and dioctyl glutarate. The composition mayfurther contain colorants such as dyes and pigments. The total amount ofthese agents may comprise from about 0.1% to 10%, from 1% to 10%, orfrom 5% to 20% of the overall composition.

The combination of two or more materials that cure by differentmechanisms, including contact with tissue or the appropriate curingenvironment for example, conditions such as aqueous, ionic, temperature,or pH, chemical crosslinking, or solvent dissipation, among others, iscontemplated by the current invention. The combination of one or morematerials that cure by one or more mechanisms combined with one ormaterials that are pre-cured or pre-formed into particles, spheres, orother structures, is also contemplated by the current invention.

The present invention contemplates the use of pre-formed solid materialssuch as particles, spheres, capsules, or the like, in combination with aliquid or semi-solid material. The pre-formed solids may comprisedegradable or resorbable materials and may have enhanced ultrasoundvisibility or may serve to enhance ultrasound visibility of thecomposite occlusive material. The particles as contemplated may benanoparticles of an average size ranging from about 100 to 2000nanometers, about 100 to 1000 nanometers, about 250 to 2000 nanometers,or about 500 to 2000 nanometers in diameter. Particles may also bemicroparticles with an average size ranging from about 0.1 to 1000micrometers, about 0.1 to 250 micrometers, about 1 to 500 micrometers,about 50-500 micrometers, about 100-750 micrometers, or about 250 to1000 micrometers. The liquid or semisolid material acts as a transportmedium for the pre-formed solids and then cures in situ, entrapping thesolids. The particles may be coated with or contained within a materialthat enhances their miscibility and/or dispersability with the liquid orsemi-solid material or minimizes the tendency of the particles topromote the premature curing of the liquid or semi-solid material priorto delivery. Coating materials may include extremely low moisturecontent formulations of the particulate constituent materials or otherpolymers or copolymers containing, for example, caprolactone,poly-β-hydroxybutyrate, delta-valerolactone, as well aspolyvinylpyrrolidone, polyamides, gelatin, albumin, proteins, collagen,poly(orthoesters), poly(anhydrides), poly(α-cyanoacrylates),poly(dihydropyrans), poly(acetals), poly(phosphazenes), poly(urethanes),poly(dioxinones), cellulose, and starches. The following patents andU.S. patent applications teach manufacturing methods for creatingechogenic particles for use in ultrasound contrast agents: U.S. Pat.Nos. 5,352,436; 5,562,099; 5,487,390; 5,955,143; 2004/0161384;2004/0258761; and 2004/0258769. Particles made by these methods arecontemplated by the present invention.

The present invention also comprises methods for sequential applicationsof the same or different materials. For example, a composition of theoccluding material that functions as the in situ curable material may beplaced in the site or sites, and an adhesive composition may be appliedseparately either before or after the curable material so as to fix theimplanted material in place, thus lowering the risk of expulsion. The insitu curable materials may cure or solidify in the native environment ofthe fallopian tube, or the curing may require the presence of an energysource, such as light, heat, other electromagnetic waves, sound waves,or microwaves or the presence of an initiator and/or accelerator forcuring. The additional energy sources may be provided by the deliverydevice or another introductory vehicle or by sources outside the body.

The end structure of a delivery catheter may have alternative shapesthat aid in maintaining the delivery end of a catheter at the site, aidin delivery of occlusive material, aid in removal of the catheter fromthe site, aid in localizing an occlusion and other shapes and designsfor functions by the end. For example, a delivery device used foroccluding the fallopian tubes in a mammal, providing a catheter havingan end that is placed within the uterine cornua at or near the tubalostia, may have end structures that comprise a shape that aids indelivery of the occlusive material, for example by maintaining thecatheter in position and preventing or minimizing the occlusive materialfrom flowing in multiple directions. This end structure may function toguide placement of the end of the catheter or anchor the catheter end toand/or cover the ostium of the tube and may take the form of a nozzle,cup, or balloon. A nozzle, cup or balloon is useful for preventing orminimizing leakage of compositions of in situ curable material away fromthe implantation site. Preferably, the end structures do not adhere tothe implantable material although the use of an absorbable, detachableend structure that may adhere to the implantable material and be left inplace after removal of the remainder of the delivery system is alsocontemplated. Using a catheter having a structure that conforms to theshape of the uterine cornua, maintaining localized delivery to at leastone ostia eliminates the need to cannulate into the fallopian tube. Endstructures comprise device elements for affecting tissues such ascautery elements, suction elements, cutting elements, scraping elements,wire elements, energy delivering elements, freezing elements or graspingelements.

The present invention comprises methods for female sterilization whereinthe delivery catheter is not inserted into the fallopian tube and inwhich the occlusive material is introduced within the uterine cornua ator near the tubal ostia affecting portions of the endometrium and/ortubal epithelium. The extent of the occlusion such as the portion of theuterine cornua and fallopian tube blocked by the occlusive material, maybe controlled by modification of the curing time, viscosity, and amountof material delivered. The current invention comprises methods foreffective blockage of a conduit, such as a fallopian tube, by occludinga minimal portion of the fallopian tube. Such occlusion may block aconduit for less than 1.0 mm of the length of the conduit, for less than1 cm of the length of the conduit, for less than 3 cm of the length ofthe conduit, for less than 5 cm of the length of the conduit, or forless than 8 cm of the length of the conduit, or to the fimbrae area. Forexample, in occluding a fallopian tube, an embodiment of the presentinvention comprises methods of application of an occluding material suchthat no more than 5 cm of the fallopian tube is occluded. In affectingthis length of tube, the anatomical areas of the fallopian tube targetedfor occlusion include the areas within the fallopian tube wall (theinterstitial segment) and early portions of the isthmic section. Thepresent invention may not be dependent on the length, width or depth ofthe solidified occluding material, and the extent of the solidifiedoccluding material may be dependent on whether subsequent reversal ofthe occlusion is desired. If reversal of the occlusion is contemplatedat the time of occluding, a minimal amount of occlusion may be achieved,thus allowing for more ease in reversing the occlusion and opening theconduit.

In one method of delivery of the occlusive material, pressure generatedin the lumen of the delivery system forces the occlusive materialthrough the delivery device, including at least one opening in at leastone delivery end, out of the device and into the area to be blocked.Once the occlusive material has been delivered, the delivery device isremoved in whole or in part from the patient (the end structure may bedetachable and fashioned from a resorbable or degradable materialdesigned to be left in place). For example, once the occlusive materialis delivered to the site or the occlusive material cures in situ, thedelivery device can be collapsed, re-folded, re-sheathed, or directlyremoved in one or more pieces from the patient.

The compositions of the present invention comprise occlusive materialsand may further comprise one or more agents that are capable ofproviding other functions, including but not limited to, a curablecarrier for the occlusive material, allowing for controlled release of asubstance, enhancing the ability of the occlusive material to causefibrosis, wound healing or similar type response or inhibitcontraception. Quinacrine is well established to create scarring of thetubal epithelium and cause tubal blockage. In combination with theocclusive material, low dosages of quinacrine or other sclerotic agents,such as tetracycline, may assist in creation of the fibrous tissueblockage or wound healing or similar type response. The compositions ofthe present invention comprise fibrous tissue growth promoting agentssuch as growth factors or pro-inflammatory reagents that are known tothose skilled in the art. U.S. Pat. No. 3,803,308 teaches that theinstillation of copper or zinc salts alone into the uterus inhibitscontraception. Current copper intrauterine devices have incorporatedthis concept. The present invention comprises compositions comprisingcopper salts or other metallic elements in addition to the occlusivematerial. Inclusion of hormonal contraceptives within the occlusivematerial to limit further the risk of pregnancy during the timeframe oftissue ingrowth or wound healing or similar type response iscontemplated.

The present invention comprises methods for using energy-deliveringdevices to initiate or completely form an occlusion. Such methodscomprise activities at the site of the placement of the occlusivematerials to aid in the formation of tissue growth or wound healing orsimilar type response and/or biodegradation or resorption of theocclusive material. Such activities include, but are not limited to, useof cautery methods, bipolar coagulating current, a high frequencygenerator to produce a tissue damaging current, and use of laser, light,microwave, and radiofrequency energy. Devices for providing suchactivities and uses thereof are taught in U.S. Pat. Nos. 4,700,701;5,095,917; 5,474,089; 5,954,715; and 6,485,486.

The present invention also comprises delivery systems, methods anddevices for removing at least one occlusion at the occluded site. Asused herein, the term reversing the occluded site, means making theconduit capable of transporting again. Making the conduit capable oftransporting can include, but is not limited to, removal of the originaloccluding material, creating a new lumen through the occluded site, suchas forming a channel through the occluding material or the in-growntissue at the occluded site, or by-passing the occluded site. Themethods of the present invention comprise delivery of devices that placepermanent plugs within one or more conduits, simultaneously orsequentially, wherein such plugs are structured such that a device ofthe present invention can be used to remove the plugs at a later time.Structures for such plugs are taught U.S. Pat. No. Re 29,345. Such plugsare not resorbable or biodegradable by bodily actions and thus mayincorporate elements for anchoring the plugs within the conduit. Theocclusion may be removed from the conduit by destruction of theoccluding material. For example, shockwaves can be used to shatter thematerial, similar to that used in lithotripsy methods, and the materialis expelled from the conduit. Chemical or biological elements, such asinstillation of solvents or enzymes, can be used to disintegrate theocclusion. Removal devices of the present invention can be used toaffect one or both fallopian tubes that have occluding material therein,by physical removal of plugs, provision of materials that recanalize theoccluding site, or that mechanically form a new channel through oraround the occluded site. The device may also deliver a stent or otherdevice to ensure that the new channel remains open. U.S. Pat. Nos.4,983,177; 5,989,580; 4,664,112 and others teach methods forreversibility of occluded sites. In methods for reversing the blockageof fallopian tubes, the present invention contemplates systems, methodsand devices that are capable of reversing the occlusion in eachfallopian tube under tactile determinations by the operator and/orimaging visualization and without removal and reinsertion or the need toreposition substantially the delivery device until one or both tubes areunblocked. The present invention contemplates methods and devices toopen the fallopian tubes one at a time, or unblock both tubes underoperator feel and/or imaging visualization and without the withdrawaland reintroduction of instrumentation, which represents an advantageover the prior art.

In one aspect of the present invention in which a partially or fullyresorbable or degradable material is used to cause occlusion of aconduit, minimal or no permanent foreign body remains in position. Infallopian tube occlusion, the occlusion is located at or near the ostiumof the tube, making non-surgical access simple. A catheter with aworking head for the removal of an occlusion in a vessel or other bodypassageway can be used with the delivery device. A method for reversalof such blocked tubes incorporates the use of a catheter-based deliverysystem similar to that used for the introduction of the occlusivematerial. In this aspect of the invention, the lumen or lumens of thedelivery device are used for the introduction of a stiff or cuttingcatheter or a catheter for instillation of a dissolution medium (e.g.,enzyme or solvent) that recanalizes the blocked section(s) of the tube.A stent or other device to maintain the opening may be placed throughthe delivery device as well.

In general, the present invention comprises methods for occluding atleast one conduit in a human or animal body, comprising, providing adelivery system capable of delivering an effective amount of acomposition comprising an occlusive material, wherein the deliverysystem comprises a delivery device comprising at least an introducershaft for providing one or more catheters; one or more catheters, acatheter comprising an end structure on a delivery end and attachmentelements on a proximal end, a composition comprising an occlusivematerial, and elements for providing the composition comprising anocclusive material into and through a catheter and delivering aneffective amount of the composition comprising an occlusive material ator near the target site such that the material occludes the lumen of theconduit; and occluding the conduit with the composition comprising anocclusive material at or within the lumen of the conduit. Elements forproviding the delivery composition include, but are not limited to,syringes and pressure systems, pumps, containers with plungers to forcematerial into the catheters, or other methods and devices for movingflowable material through a catheter or tube. The methods furthercomprise opening conduits, whether the conduit is occluded by methods ofthe present invention or by other methods or processes, includingnatural and synthetic or medical processes. The methods may compriseopening two conduits without removal and re-introduction or substantialrepositioning of the introducer shaft. Such a method may be used totreat fallopian tubes of a mammal.

The compositions used in the methods of the present invention comprisingthe occlusive material may be mixed prior to delivery to the lumen. Thecompositions may comprise a tissue adhesive and a solvated polymer, or apolymer that is soluble in the adhesive wherein the composition cures insitu. The composition comprising the occlusive material may beultrasound visible. The ultrasound visible material may comprisemicrobubbles of air or other gases or microparticles of a material thatentrap air or other gases. Compositions of the present inventioncomprise compositions wherein the tissue adhesive is cyanoacrylate,polyacrylic acids, polyethylene glycols, modified polyethylene glycols,thrombin, collagen, collagen-based adhesives, fibrin, fibrin gluecompositions, gelatin-resorcinol-formaldehyde-glutaraldehye (GRFG) glue,autologous blood in combination with collagen or thrombin, crosslinkedalbumin adhesives, modified glycosaminiglycans,poly(N-isopropylacrylamide)-based adhesives, alginates, or chitosan orgelatin, crosslinked with carbodiimide or genepin; and the solvatedpolymer is a resorbable polyester, including polylactide, polyglycolide,or polycaprolactone or copolymers of these materials, includingpoly(lactide-glycolide) acid (PLGA) or poly(lactide-co-ε-caprolactone)(PLCL). The compositions may be visible by ultrasound. The compositionsmay further comprise tissue scarring agents, fibrosis agents,fertilization inhibitors, contraceptive agents, tissue growth or woundhealing promoters, hormones, polymerization inhibitors, polymerizationstabilizers, emulsifying agents, echogenic agents, contrast agents,viscosity-modifying materials, plasticizers, colorants or combinationsthereof.

The cured compositions of the present invention swell less than 20%, andmay be about 20% to about 100% substantially resorbed or degraded in arange of about 30 to about 365 days. Once resorbed or degraded theocclusion may be maintained by tissue ingrowth or wound healing responseor similar type response.

Compositions of the present invention may also comprise a tissueadhesive and particles. The particles may be nano- or micro-particlescomprising spheres of resorbable polymers. The particles may be fromabout 0.1 micrometer to about 1000 micrometers in diameter. Thecompositions may be viewable by ultrasound or imaging techniques. Thecompositions may further comprise a curable carrier for the occlusivematerials, a control release agent, tissue scarring agents, woundhealing promoting agents, fibrosis agents, fertilization inhibitors,contraceptive agents, tissue growth promoters, hormones, polymerizationinhibitors, polymerization stabilizers, emulsifying agents, echogenicagents, contrast agents, viscosity-modifying materials, plasticizers,colorants or combinations thereof.

The present invention comprises methods for contraception comprisingproviding a delivery system capable of delivering an effective amount ofa composition comprising an occlusive material, wherein the deliverysystem comprises a delivery device comprising at least an introducershaft for providing one or more catheters; one or more catheters, suchas a dual lumen balloon catheter; a composition comprising an occlusivematerial and elements for providing the composition comprising anocclusive material into and through the catheters; delivering aneffective amount of the composition comprising an occlusive material ator near the target location such that the material occludes the lumen ofat least one fallopian tube; and occluding the fallopian tube with thecomposition comprising an occlusive material at or within the lumen ofthe conduit.

The present invention comprises devices, including contraceptivedevices, and methods of using such devices comprising an introducershaft having at least one exit port, or only one exit port, forproviding at least one catheters; at least one catheter, a catheter maycomprise an end structure at the delivery end, or may compriseattachment elements at the proximal end, or both, the device may furthercomprise a composition comprising an occlusive material, and elementsfor providing the composition comprising an occlusive material into andthrough the catheters. The end structure of a catheter may be a cup,nozzle, or a balloon. The devices may further comprise a delivery devicestabilizer for holding the contraceptive device in place oncepositioned. The delivery device stabilizer may fit over or attach to thecervix or fit into or expand within the cervix to hold the device inposition.

Methods of the present invention comprise providing an occludingcomposition to a conduit, for example, a fallopian tube of a human orother mammal. Methods of the present invention comprise methods ofcontraception. The devices of the present invention are used to deliverthe occluding composition to the uterine cornua adjacent to a fallopiantube, and occluding the fallopian tube. Once the introducer shaft of thedevice is in place, it is not moved, other than rotation of the shaft toposition the exit port opening toward the second fallopian tube.

The occluding compositions of the present invention comprise a tissueadhesive, and the occluding compositions cure in situ, once in place inthe conduit. It is preferred that the occluding compositions beultrasound visible, either before or after curing, or both. Ultrasoundvisible materials may be added to occluding compositions, and includemicrobubbles of air or gas or microparticles of a material that entrapair or gas. The tissue adhesive may comprise one or more cyanoacrylates,polyacrylic acids, polyethylene glycols, modified polyethylene glycols,thrombin, collagen, collagen-based adhesives, fibrin, fibrin gluecompositions, gelatin-resorcinol-formaldehyde-glutaraldehye (GRFG) glue,autologous blood in combination with collagen or thrombin, crosslinkedalbumin adhesives, modified glycosaminiglycans,poly(N-isopropylacrylamide)-based adhesives, alginates, or chitosan orgelatin, crosslinked with carbodiimide or genepin or combinationsthereof. The cured occluding composition swells less than 20%. The curedoccluding composition may be about 20% to about 100% substantiallyresorbed or degraded in a range of about 30 to about 90 days. After orduring the resorption or degradation of the occluding composition, theocclusion is maintained by tissue ingrowth or wound healing or a similartype response. The occluding composition may further comprise polymersor particles or both. The particles may be nano- or micro-particles.

The present invention also comprises systems and methods for openingoccluded conduits. A method comprises providing a delivery devicecomprising an introducer shaft having at least one exit port, or onlyone exit port, for providing at least one catheters; at least onecatheter, a catheter may comprise an end structure at the delivery end,or may comprise attachment elements at the proximal end, and maycomprise elements for re-opening the conduit; and re-opening or openingthe conduit. Elements for opening the conduit comprise devices ormembers for providing shockwaves to shatter the occluding material,chemical elements including solvents, biological elements includingenzymes, or mechanical elements including stiff or cutting catheter endsto recanalize the lumen. The method may further comprise maintaining theopening of the conduit by providing a stent within the lumen of theconduit.

The present invention comprises methods and devices that allow for theone-time penetration of the cervix, comprising an introducer shaft,which functions to orient delivery catheters in three dimensional space.The atraumatic tip of the introducer shaft is provided through thecervix and into the uterine cavity. Once the tip is located at theuterine fundus, and optionally stabilized by stabilization elements, acatheter may be advanced through the introducer shaft and the deliveryend of the catheter exits the single exit port. The catheter may be usedto provide occluding compositions or the delivery of materials ordevices for re-opening an occluded conduit, such as a fallopian tube.After the appropriate action, such as occlusion or re-opening, thecatheter is retracted so that the delivery end of the catheter is withinthe introducer shaft or may be removed from the introducer entirely. Theintroducer shaft is then rotated so that the single exit port is nowopen toward the untreated uterine cornua. The delivery device is notremoved from the patient, such as by withdrawal through the cervix aftertreatment at one fallopian tube, and may not have been repositionedother than by rotation. A catheter, such as the original catheter or anew catheter, is advanced through the single exit port and the occludingcomposition or materials or devices for re-opening an occluded fallopiantube are provided at or near the uterine cornua or at or near theopening of the fallopian tube. Once the delivery is completed, thecatheter is retracted into the shaft, and if used, a stabilizing deviceis disengaged, and the introducer shaft is retracted from the uterinecavity, through the cervix and to the exterior of the patient.

The introducer shaft allows for separation of the uterine walls, forpositioning at the fundus of the uterus (the top portion of the uterus),and orientation of one or more catheters to the fallopian tubes. Thecatheter, such as a balloon catheter, may be of a length that allows forvariation in uterine sizes. The introducer shaft may be of a length thatallows for advancement into varying lengths of uterine cavities.Alignment of the catheters with the tubal ostia is provided by theorientation of one or more exit ports, wherein such orientation directsthe catheters in a generally perpendicular fashion to the ostia. Priorart devices do not provide for a flexible system that can orient acatheter to a particular location in the uterus without visualizationmeans such as a hysteroscope.

It must be noted that, as used in this specification and the appendedclaims, the singular forms “a”, “an”, and “the” include plural referentsunless the context clearly dictates otherwise.

All patents, patent applications and references included herein arespecifically incorporated by reference in their entireties.

It should be understood, of course, that the foregoing relates only toexemplary embodiments of the present invention and that numerousmodifications or alterations may be made therein without departing fromthe spirit and the scope of the invention as set forth in thisdisclosure.

Although the exemplary embodiments of the present invention describe indetail methods, delivery systems, and compositions to occlude thefallopian tubes of human, the present invention is not limited to theseembodiments. There are numerous modifications or alterations that maysuggest themselves to those skilled in the art for use of the methods,delivery systems, and compositions herein for the occlusion of a varietyof conduits in both human and non-human mammals.

The present invention is further illustrated by way of the examplescontained herein, which are provided for clarity of understanding. Theexemplary embodiments should not to be construed in any way as imposinglimitations upon the scope thereof. On the contrary, it is to be clearlyunderstood that resort may be had to various other embodiments,modifications, and equivalents thereof which, after reading thedescription herein, may suggest themselves to those skilled in the artwithout departing from the spirit of the present invention and/or thescope of the appended claims.

EXAMPLES Example 1 Preparation of Occlusive Material A

A solution of 25/75 poly lactide-co-ε-caprolactone (PLCL) was prepared50% by weight in n-methyl-pyrrolidone (NMP) and sterilized. A mixture of2-methoxypropyl cyanoacrylate (MPCA) with a biocompatible acid, in thiscase glacial acetic acid (AA), was prepared containing approximately 1part MPCA and 1 part AA and sterilized. Implantable material A wasprepared immediately prior to use by mixing 0.8 cc PLCL solution with0.2 cc MPCA mixture until homogeneity of the mixture was achieved. Theresultant mixture initially warms indicative of curing but remainsadhesive to tissue and flowable through a 20G IV catheter for at least15 min at room temperature in the absence of an aqueous environment. Incontact with either water or animal tissue, the implantable materialcompletes its curing quickly, forming a semi-solid material that iscompressible and flakes relatively easily.

Example 2 Preparation of Occlusive Material B

A solution of 50150 poly lactide-co-glycolide (PLGA) was prepared 25% byweight in ethyl alcohol (EtOH) and sterilized. A mixture of butylcyanoacrylate (BCA) with AA was prepared containing approximately 2parts BCA and 1 part AA and sterilized. Implantable material B wasprepared immediately prior to use by mixing 0.4 cc PLGA solution with0.4 cc BCA mixture until homogeneity of the mixture was achieved. Theresultant mixture initially warms indicative of curing but remainsstrongly adhesive to tissue and flowable through a 20G IV catheter forat least 15 min at room temperature in the absence of an aqueousenvironment. In contact with either water or animal tissue, theimplantable material completes its curing quickly, forming a relativelyincompressible semi-solid material that fractures on attempted bending.

Example 3 Preparation of Occlusive Material C

Particles of 50/50 PLGA were prepared by dissolving PLGA in methylenechloride to create a 25% weight/volume solution, emulsifying in a 0.3%polyvinyl alcohol (PVA) solution, and further addition of PVA solutionwith 2% isopropyl alcohol to remove solvent. Particles were collected,lyophilized, and sterilized. Particles (0.25 g) were added to 0.75 g ofa sterilized mixture containing 2 parts BCA and one part AA. Theresulting particulate suspension was flowable at room temperature butcured on contact with water or animal tissue, forming a stiff, adherentmaterial.

Example 4 Preparation of Occlusive Material D

Particles of 50/50 PLGA were prepared as described in Example 3 with theaddition of hydroquinone (0.5%) to the PVA emulsification, resulting inthe entrapment of hydroquinone on the surface of the particles. Theparticles were collected, lyophilized, and sterilized. Particles (0.25g) were added to 0.75 g of sterilized BCA. The particulate suspensionremained flowable at room temperature with no indication ofcyanoacrylate polymerization. The composition hardened on exposure towater or tissue, forming a stiff, adherent material.

Example 5 Study of Occlusive Materials in the Rabbit Fallopian Tube

Fourteen candidate materials prepared similarly to the previous exampleshave been studied for their ability to create a mechanical occlusion andgenerate a tissue ingrowth response when placed into the fallopian tubesof rabbits. One of the materials, methyl cyanoacrylate (MCA), has ahistory of use in effecting female sterilization in animals and humansbut was shown to have an unacceptable biocompatibility profile and wasused as a control in one of the studies. Each of the test and controlmaterials was placed into the fallopian tubes of seventy-four NewZealand white rabbits through an open procedure in which a 20G IVcatheter or a modified delivery system catheter was used as the deliverysystem. Materials were infused through the catheter into the cornualaspect of the right and left uterine body; finger pressure or atraumaticclamps were used to prohibit backward flow of the material into theremainder of the uterine horn. Forward flow of the material was stoppedonce materials were seen within the cul-de-sac (i.e., peritoneal spillhad occurred) or the full volume of material had been delivered or thematerial was stopped by another atraumatic clamp. It was noted that, incomparison to the control material which cured very rapidly, sticking tothe catheter, and with a high heat of curing, the test materials had alonger curing timeframe (within the time prior to closure butsufficiently long to remove the catheters without adhesion) and did notgenerate as much heat. Once both right and left tubes had been treated,the reproductive organs were repositioned within the pelvis, and theincision was closed. At various time points from 1 day to 2 months, theanimals were sacrificed. At times, dye infusion testing was used todemonstrate that the fallopian tubes of all animals were blocked. Testmaterials that generated an excessive amount of inflammation andadhesions or to benign of a reaction were ruled out. The remaining testmaterials and the control generated an appropriate tissue response,completely blocking the lumen of the fallopian tube with inflammatorycells and debris. Test materials may have contained a plasticizer, suchas ATC and stabilizers, such as BHA as indicated in the table below.Approximate percentage of each component is indicated.

Test Material Compositions

Component A Component B Additive(s) Additive(s) 100% MCA- Control 35%nBCA 25% 50/50 PLGA Lactic Acid & NMP 40% nBCA 10% 27/75 PLGA LacticAcid & NMP 40% nBCA 10% 80/20 PLGA Lactic Acid & NMP 40% nBCA 10% 50/50PLGA 15% nBCA 65% MIPCA 10% 50/50 PLGA BHA & ATC 15% nBCA 65% MIPCA 10%85/15 PLGA BHA & ATC 85% MIPCA 10% 50/50 PLGA BHA & ATC 85% MIPCA 10%85/15 PLGA BHA & ATC 70% MCA 20% MIPCA 10% 85/15 PLGA BHA 70% MCA 30%MCA BHA 50% MCA 50% MIPCA 5% 85/15 PLGA BHA 40% MCA 60% MIPCA BHA 30%MCA 70% MIPCA 5% 85/15 PLGA BHA

Example 6 Use of the Delivery System in Explanted Human Uteri

A prototype delivery system comparable to that shown in FIG. 1 was usedto deliver dye and occlusive material to the fallopian tubes of threeexplanted human uteri obtained in accordance with the rules of theinstitution's Institutional Review Board. In each case, the explanteduterus was placed on an examination table in anatomic position, and theshaft of the introducer was placed transcervically until the tip reachedthe top of the uterine fundus as determined by tactile feel. Each of twoballoon catheters was then advanced through the lumen in the introduceruntil it was felt to lodge within the cornual aspect of the uterus. Theballoons were inflated until resistance was felt. The uterus was thenbivalved to allow for visualization of the device, which, in each case,was seen to be appropriately placed. One case represented a normal,multiparous uterus, while two cases demonstrated significantleiomyomatous pathology, indicating that the presence of fibroidsoutside the midline or the cornua does not interfere with the successfuluse of the delivery system. After successful placement was confirmed, aseries of liquid injections through the catheters was conducted; firstwith saline to confirm patency, second with a hematoxylin dye todemonstrate that backflow into the uterine cavity did not occur, andfinally with an occlusive material from the animal study in the previousexample to demonstrate full functionality of the system in humans. Ineach case tested, dye demonstrated forward flow without leakage into theuterine cavity, and the material was successfully delivered.

Example 7 Occluding Compositions

Functionality Component A Component B Additive(s) of additive 50%Gelatin- 50% Formaldehyde- resorcinol glutaraldehyde 50% Gelatin- 50%Formaldehyde- Microbubbles Ultrasound resorcinol glutaraldehyde of airvisibility 50% Gelatin- 50% Formaldehyde- Progesterone- Inhibition ofresorcinol glutaraldehyde estrogen- ovulation dissolved in duringcomponent B maturation of blockage 50% Gelatin- 50% Formaldehyde-Tetracyline- Promotion of resorcinol glutaraldehyde dissolved inscarring or component B fibrosis 50% Gelatin- 50% Formaldehyde- bFGF,EGF- Induction of resorcinol glutaraldehyde dissolved in tissuecomponent B ingrowth or wound healing 50% Gelatin- 50% Formaldehyde-Gold particles X-ray resorcinol glutaraldehyde suspended in visibilitycomponent A 50% Gelatin- 50% Formaldehyde- Copper Inhibition ofresorcinol glutaraldehyde sulfate- ovulation and/ dissolved or orenhanced suspended in MRI visibility component A 70% Fibrin glue 30%poly-L-lactide dissolved 50% by weight in NMP 70% Fibrin glue 30%poly-L-lactide Microbubbles Ultrasound dissolved 50% by of airvisibility weight in NMP 70% Fibrin glue 30% poly-L-lactideProgesterone- Inhibition of dissolved 50% by estrogen- ovulation weightin NMP dissolved in during component B maturation of blockage 70% Fibringlue 30% poly-L-lactide Tetracyline- Promotion of dissolved 50% bydissolved in scarring or weight in NMP component B fibrosis 70% Fibringlue 30% poly-L-lactide bFGF, EGF- Induction of dissolved 50% bydissolved in tissue weight in NMP component B ingrowth or wound healing70% Fibrin glue 30% poly-L-lactide Gold particles X-ray dissolved 50% bysuspended in visibility weight in NMP component A 70% Fibrin glue 30%poly-L-lactide Copper Inhibition of dissolved 50% by sulfate- ovulationand/ weight in NMP dissolved or or enhanced suspended in MRI visibilitycomponent A 11% n-butyl 89% poly-DL-lactide- cyanoacrylate co-glycolidedissolved 50% by weight in NMP 11% n-butyl 89% poly-DL-lactide-Microbubbles Ultrasound cyanoacrylate co-glycolide dissolved of airvisibility 50% by weight in NMP 11% n-butyl 89% poly-DL-lactide- 10%lactic Inhibition of cyanoacrylate co-glycolide dissolved acid, poly-50% by weight in NMP Microbubbles merization, of air Ultrasoundvisibility 11% n-butyl 89% poly-DL-lactide- Progesterone- Inhibition ofcyanoacrylate co-glycolide dissolved estrogen- ovulation 50% by weightin NMP dissolved in during component B maturation of blockage 11%n-butyl 89% poly-DL-lactide- Tetracyline- Promotion of cyanoacrylateco-glycolide dissolved dissolved in scarring or 50% by weight in NMPcomponent B fibrosis 11% n-butyl 89% poly-DL-lactide- bFGF, EGF-Induction of cyanoacrylate co-glycolide dissolved dissolved in tissue50% by weight in NMP component B ingrowth or wound healing 11% n-butyl89% poly-DL-lactide- Gold particles X-ray cyanoacrylate co-glycolidedissolved suspended in visibility 50% by weight in NMP component A 11%n-butyl 89% poly-DL-lactide- Copper Inhibition of cyanoacrylateco-glycolide dissolved sulfate- ovulation and/ 50% by weight in NMPdissolved or or enhanced suspended in MRI visibility component A 33% 67%poly-DL-lactide- methoxypropyl co-glycolide dissolved cyanoacrylate 50%by weight in NMP 33% 67% poly-DL-lactide- Microbubbles Ultrasoundmethoxypropyl co-glycolide dissolved of air visibility cyanoacrylate 50%by weight in NMP 31% 62% poly-DL-lactide- 7% lactic acid, Inhibition ofmethoxypropyl co-glycolide dissolved Microbubbles poly- cyanoacrylate50% by weight in NMP of air merization, Ultrasound visibility 33% 67%poly-DL-lactide- Progesterone- Inhibition of methoxypropyl co-glycolidedissolved estrogen- ovulation cyanoacrylate 50% by weight in NMPdissolved in during component B maturation of blockage 33% 67%poly-DL-lactide- Tetracyline- Promotion of methoxypropyl co-glycolidedissolved dissolved in scarring or cyanoacrylate 50% by weight in NMPcomponent B fibrosis or wound healing 33% 67% poly-DL-lactide- bFGF,EGF- Induction of methoxypropyl co-glycolide dissolved dissolved intissue cyanoacrylate 50% by weight in NMP component B ingrowth or woundhealing 33% 67% poly-DL-lactide- Gold particles X-ray methoxypropylco-glycolide dissolved suspended in visibility cyanoacrylate 50% byweight in NMP component A 33% 67% poly-DL-lactide- Copper Inhibition ofmethoxypropyl co-glycolide dissolved sulfate- ovulation and/cyanoacrylate 50% by weight in NMP dissolved or or enhanced suspended inMRI visibility component A 11% isohexyl 89% poly-DL-lactide-cyanoacrylate co-ε-co-caprolactone dissolved 50% by weight in ethylalcohol 11% isohexyl 89% poly-DL-lactide- Microbubbles Ultrasoundcyanoacrylate co-ε-co-caprolactone of air visibility dissolved 50% byweight in ethyl alcohol 10% isohexyl 80% poly-DL-lactide- 10% aceticInhibition of cyanoacrylate co-ε-co-caprolactone acid, poly- dissolved50% by Microbubbles merization, weight in ethyl alcohol of airUltrasound visibility 11% isohexyl 89% poly-DL-lactide- Progesterone-Inhibition of cyanoacrylate co-ε-co-caprolactone estrogen- ovulationdissolved 50% by dissolved in during weight in ethyl alcohol component Bmaturation of blockage 11% isohexyl 89% poly-DL-lactide- Tetracyline-Promotion of cyanoacrylate co-ε-co-caprolactone dissolved in scarring ordissolved 50% by component B fibrosis or weight in ethyl alcohol woundhealing 11% isohexyl 89% poly-DL-lactide- bFGF, EGF- Induction ofcyanoacrylate co-ε-co-caprolactone dissolved in tissue dissolved 50% bycomponent B ingrowth weight in ethyl alcohol or wound healing 11%isohexyl 89% poly-DL-lactide- Gold particles X-ray cyanoacrylateco-ε-co-caprolactone suspended in visibility dissolved 50% by componentA weight in ethyl alcohol 11% isohexyl 89% poly-DL-lactide- CopperInhibition of cyanoacrylate co-ε-co-caprolactone sulfate- ovulation and/dissolved 50% by dissolved or or enhanced weight in ethyl alcoholsuspended in MRI visibility component A 60% n-butyl 40% poly-DL-lactide-cyanoacrylate co-glycolide microparticles emulsified in 4% polyvinylalcohol 60% n-butyl 40% poly-DL-lactide- Microbubbles Ultrasoundcyanoacrylate co-glycolide of air visibility microparticles emulsifiedin 4% polyvinyl alcohol 60% n-butyl 30% poly-DL-lactide- 10% lacticInhibition of cyanoacrylate co-glycolide acid, poly- microparticlesMicrobubbles merization, emulsified in 4% of air Ultrasound polyvinylalcohol visibility 60% n-butyl 40% poly-DL-lactide- Progesterone-Inhibition of cyanoacrylate co-glycolide estrogen- ovulationmicroparticles dissolved in during emulsified in 4% component Amaturation of polyvinyl alcohol blockage 60% n-butyl 40%poly-DL-lactide- Quinacrine- Promotion of cyanoacrylate co-glycolidedissolved in scarring of microparticles component A fibrosis oremulsified in 4% wound polyvinyl alcohol healing 60% n-butyl 40%poly-DL-lactide- BFGF, EGF- Induction of cyanoacrylate co-glycolidedissolved in tissue microparticles component B ingrowth or emulsified in4% wound polyvinyl alcohol healing 60% n-butyl 40% poly-DL-lactide- Goldparticles X-ray cyanoacrylate co-glycolide suspended in visibilitymicroparticles component A emulsified in 4% polyvinyl alcohol 60%n-butyl 40% poly-DL-lactide- Copper Inhibition of cyanoacrylateco-glycolide sulfate- ovulation and/ microparticles dissolved or orenhanced emulsified in 4% suspended in MRI visibility polyvinyl alcoholcomponent A 70% 30% methoxyisopropyl Stabilizer Induction ofmethoxypropyl cyanoacrylate tissue cyanoacrylate ingrowth or woundhealing 50% 50% methoxyisopropyl Stabilizer Induction of methoxypropylcyanoacrylate tissue cyanoacrylate ingrowth or wound healing 30% 70%methoxyisopropyl Stabilizer Induction of methoxypropyl cyanoacrylatetissue cyanoacrylate ingrowth or wound healing 60% 40% methoxyisopropylStabilizer Induction of methoxypropyl cyanoacrylate tissue cyanoacrylateingrowth or wound healing 70% methyl 30% methoxyisopropyl StabilizerInduction of cyanoacrylate cyanoacrylate tissue ingrowth or woundhealing 50% methyl 50% Stabilizer Induction of cyanoacrylatemethoxyisopropyl tissue cyanoacrylate ingrowth or wound healing 30%methyl 70% Stabilizer Induction of cyanoacrylate methoxyisopropyl tissuecyanoacrylate ingrowth or wound healing 60% methyl 40% StabilizerInduction of cyanoacrylate methoxyisopropyl tissue cyanoacrylateingrowth or wound healing 98% 2% methoxy Stabilizer Induction ofmethoxypropyl isopropyl tissue cyanoacrylate cyanoacetate ingrowth orwound healing 95% 5% methoxy Stabilizer Induction of methoxypropylisopropyl tissue cyanoacrylate cyanoacetate ingrowth or wound healing90% 10% methoxy Stabilizer Induction of methoxypropyl isopropyl tissuecyanoacrylate cyanoacetate ingrowth or wound healing 80% 20% methoxyStabilizer Induction of methoxypropyl isopropyl tissue cyanoacrylatecyanoacetate ingrowth or wound healing 69:29% 2% methoxy StabilizerInduction of methoxy- isopropyl tissue propyl:methoxy- cyanoacetateingrowth or isopropyl wound healing cyanoacrylate 67:28% 5% methoxyStabilizer Induction of methoxy- isopropyl tissue propyl:methoxy-cyanoacetate ingrowth or isopropyl wound healing cyanoacrylate 65:25%10% methoxy Stabilizer Induction of methoxy- isopropyl tissuepropyl:methoxy- cyanoacetate ingrowth or isopropyl wound healingcyanoacrylate 60:20% 20% methoxy Stabilizer Induction of methoxy-isopropyl tissue propyl:methoxy- cyanoacetate ingrowth or isopropylwound healing cyanoacrylate 49:49% 2% methoxy Stabilizer Induction ofmethoxy- isopropyl tissue propyl:methoxy- cyanoacetate ingrowth orisopropyl wound healing cyanoacrylate 47:48% 5% methoxy StabilizerInduction of methoxy- isopropyl tissue propyl:methoxy- cyanoacetateingrowth or isopropyl wound healing cyanoacrylate 45:45% 10% methoxyStabilizer Induction of methoxy- isopropyl tissue propyl:methoxy-cyanoacetate ingrowth or isopropyl wound healing cyanoacrylate 40:40%20% methoxy Stabilizer Induction of methoxy- isopropyl tissuepropyl:methoxy- cyanoacetate ingrowth or isopropyl wound healingcyanoacrylate 70% 30% methyl Stabilizer Induction of methoxypropylcyanoacrylate tissue cyanoacrylate ingrowth or wound healing 50% 50%methyl Stabilizer Induction of methoxypropyl cyanoacrylate tissuecyanoacrylate ingrowth or wound healing 70% 30% methyl StabilizerInduction of methoxyisopropyl cyanoacrylate tissue cyanoacrylateingrowth or wound healing 50% 50% methyl Stabilizer Induction ofmethoxyisopropyl cyanoacrylate tissue cyanoacrylate ingrowth or woundhealing

Example 8 Use of the Delivery System in Human Subjects

A delivery system comparable to that shown in FIG. 1 was used to delivereither dye or an occlusive material to the fallopian tubes of sixty-fivehuman subjects in accordance with the rules of the institution'sInstitutional Review Board. In cases where only dye was provided throughthe delivery system to the fallopian tubes, an evaluation of deliverysystem placement was confirmed with the introducer at the fundus and theballoon catheters at each cornua. Dye was confirmed to exit out eachfallopian tube as was evidenced by fluoroscopy. In some instances, onefallopian tube was assessed followed by the assessment of the other. Inother instances, both fallopian tubes were assessed simultaneously. Forcases where occlusive material was presented through the delivery systemto the fallopian tubes, the subjects underwent a full hysterectomyprocedure (removal of the uterus with fallopian tubes intact) forevaluation up to one month following the delivery of the occlusivematerial. Placement of the delivery system and occlusive material wasperformed with tactile feel and successful placement was confirmed byvisual evaluation of the uterine cavity and fallopian tubes on anexamination table once removed from the subject. Some patients presentedwith abnormalities that precluded the placement of the introducer at thefundus and subsequent advancement of the balloon catheters to thecornua. In certain cases, prior to removal of the patient's reproductiveorgan, a study was performed with contrast medium to confirm fallopiantube blockage. Full histopathological evaluation was performed onpatients that received the procedure and returned approximately onemonth post the placement of the occlusive material. Occlusive materialsachieved complete (100%) fallopian tube blockage over a length of thefallopian tube. Different occlusive materials created varying degrees ofocclusion.

Example 9 Occluding Compositions with Degradation Evaluated

Solutions containing various percentages of cyanoacrylates, such asmethyl cyanoacrylate (MCA), methoxy isopropyl cyanoacrylate (MIPCA),methoxy propyl cyanoacrylate (MPCA), ethoxy ethyl cyanoacrylate (EECA),methoxy ethyl cyanoacrylate (MECA), n-butyl cyanacrylate (nBCA), octylcyanoacrylate (OCA) with plasticizers (additives) with or without PolyLactic Glycolic Acid (PLGA) were used. Approximately 0.6 grams of eachformulation, simulating the amount being provided to the fallopian tube,were applied to a natural wool disc of approximately ¼ inch by 1 inchdisc, simulating a protenacious environment to polymerize. The treateddisc was immersed in a test tube or centrifuge tube containing 40 ml, ofa buffered saline solution, pH 7.4 simulating the human or animalenvironment. The containers were sealed and immersed in constanttemperature environments at 37° C., or normal body temperature. Theinvestigated samples were weighed to determine the exact amount offormula deposited on each treated disc. The containers were subjected toslow agitation, simulating peristaltic motion in the fallopian tubes.The samples were held at the specified temperature for a period of timeas noted in the tables below. Upon the desired time expiration, thebuffer was discarded and the container was transferred to a vacuumchamber fitted with a vacuum pump capable of drawing down to 100-500millitorr. The containers were subjected to evacuation for a time periodsufficient to achieve constant weight at room temperature. Theeffectiveness of each composition was determined by the degree ofmaterial loss after the specified times of immersion and compared tocontrol conditions. Data points are averaged.

Fourteen Day Study

Cyanoacrylate Additive % Loss 100%  nBCA 5 100%  OCA 6 100%  MCA 13100%  MIPCA 16 100%  MPCA 32 100%  EECA 33 95% MIPCA  5% AcetylTricitrate 25 (ATC) 95% MIPCA  5% Glycerol Tricitrate 27 (GTA) 95% MIPCA 5% Methyl Cyanoacetate 23 (MCYA) 95% MIPCA  5% Vitamin E Acetate 15(VEA) 95% MIPCA  5% 85:15 Poly Lactic 27 Glycolic Acid (PLGA) 95% MIPCA 5% VEA 29 95% EECA  5% ATC 34 95% EECA  5% GTA 36 95% EECA  5% MCYA 3695% EECA  5% VEA 31 95% EECA  5% 85:15 PLGA 31 95% MECA  5% ATC 22 95%MECA  5% GTA 23 95% MECA  5% MCYA 21 95% MECA  5% 85:15 PLGA 13 95% MCA 5% ATC 17 95% MCA  5% GTA 16 95% MCA  5% MCYA 16 95% MCA  5% VEA 26 95%MCA  5% 85:15 PLGA 16 95% MCA  5% MCYA 18 90% MCA 10% MCYA 24 85% MCA15% MCYA 27 80% MCA 20% MCYA 31 50% MCA 50% MCYA 62 95% MCA  5%Polyethylene glycol 14 dimethyl ether (PEG DME) 95% MCA  5% MCYA 19 80%MCA 20% MCYA 31 50% MCA 50% MCYA 83 95% MCA  5% PEGDME 17 95% MCA  5%50:50 PLGA 16 90% MCA 10% 50:50 PLGA 17 95% MCA  5% 85:15 PLGA 17 90%MCA 10% 85:15 PLGA 13 95% MCA  5% Nitromethane 19 90% MCA 10%Nitromethane 23 95% MCA  5% Propylene Carbonate 13 90% MCA 10% PropyleneCarbonate 17 80% MCA 20% Propylene Carbonate 30 95% MCA  5% EthyleneCarbonate 18 90% MCA 10% Ethylene Carbonate 24 80% MCA 20% EthyleneCarbonate 29 95% MCA  5% Dioctyl Adipate 11 90% MCA 10% Dioctyl Adipate12 80% MCA 20% Dioctyl Adipate 14 95% MCA  5% Dibutyl Adipate 11 90% MCA10% Dibutyl Adipate 13 80% MCA 20% Dibutyl Adipate 16 95% MCA  5% ButylAcetate 17 90% MCA 10% Butyl Acetate 23 80% MCA 20% Butyl Acetate 36 95%MCA  5% Ethyl Acetate 17 90% MCA 10% Ethyl Acetate 26 80% MCA 20% EthylAcetate 31 95% MCA  5% Ethyl Formate 17 90% MCA 10% Ethyl Formate 22 80%MCA 20% Ethyl Formate 29 95% MCA  5% Methyl Acetate 22 90% MCA 10%Methyl Acetate 24 80% MCA 20% Methyl Acetate 31 95% MCA  5% Methyl EthylKetone 19 90% MCA 10% Methyl Ethyl Ketone 24 80% MCA 20% Methyl EthylKetone 33 90% nBCA 10% MCYA 20 80% nBCA 20% MCYA 29 60% nBCA 40% MCYA 3790% nBCA 10% nButyl Cyanoacetate 11 (nBCYA) 80% nBCA 20% nBCYA 19 60%nBCA 40% nBCYA 36 90% MIPCA 10% MCYA 20 80% MIPCA 20% MCYA 33 60% MIPCA40% MCYA 69 90% MIPCA 10% Methoxy Isopropyl 75 cyanoacetate (MIPCYA) +additive 80% MIPCA 20% MIPCYA + additive 82 60% MIPCA 40% MIPCYA +additive 89 98% nBCA  2% Ethylene Carbonate 9 95% nBCA  5% EthyleneCarbonate 10 90% nBCA 10% Ethylene Carbonate 15 98% OCA  2% EthyleneCarbonate 8 95% OCA  5% Ethylene Carbonate 12 90% OCA 10% EthyleneCarbonate 16 95% MCA  5% Trioxane (TOX) 17 90% MCA 10% Trioxane 15 80%MCA 20% Trioxane 30 80% MCA 20% Phthalic Anhydride 15 80% MCA 20% MaleicAnhydride 40 98% MIPCA  2% Ethylene Carbonate 14 95% MIPCA  5% EthyleneCarbonate 17 90% MIPCA 10% Ethylene Carbonate 21 80% MIPCA 20% EthyleneCarbonate 33 85% NBCA 15% Ethylene Carbonate 19 80% NBCA 20% EthyleneCarbonate 24 98% MPCA  2% Ethylene Carbonate 30 95% MPCA  5% EthyleneCarbonate 30 90% MPCA 10% Ethylene Carbonate 38 80% MPCA 20% EthyleneCarbonate 47 95% MCA  5% Ethylene Carbonate 16 90% MCA 10% EthyleneCarbonate 20 80% MCA 20% Ethylene Carbonate 27 98% MIPCA  2% MIPCYA 3995% MIPCA  5% MIPCYA 57 90% MIPCA 10% MIPCYA 68 90% MCA 10% MIPCYA 1680% MCA 20% MIPCYA 24 95% MCA  5% Ethyl Acetoacetate 18 90% MCA 10%Ethyl Acetoacetate 22 95% MIPCA  5% Ethyl Acetoacetate 32 90% MIPCA 10%Ethyl Acetoacetate 49 95% 3MPCA  5% Ethyl Acetoacetate 42 90% 3MPCA 10%Ethyl Acetoacetate 57Thirteen Day Study

Cyanoacrylate Additive % Loss 100%  MPCA 33 80% MIPCA 20% TOX 29 80%MPCA 20% TOX 54 70:05:20% MPCA  5:20% MA:TOX 76 90% MCA 10% MaleicAnhydride 35 (MA) 70:10:20% MCA 10:20% MA:TOX 53 70:5:20% MCA  5:20%MA:TOX 47 80% MCA 20% TOX 27 95% MPCA  5% Maleic Anhydride 58 80% MCA20% Maleic Anhydride 43 95% MIPCA  5% Maleic Anhydride 54 100%  MCA 1000PPM SO2 15 90 MIPCA 10% MIPCYA 19 80 MIPCA 20% MIPCYA 33 70 MIPCA 10:20%MIPCYA:TOX 42 90 MPCA 10% MIPCYA 43 80 MPCA 20% MIPCYA 62 70% MPCA10:20% MIPCYA:TOX 66 80 MCA 20% MIPCYA 21Seven Day Study

Cyanoacrylate Additive % Loss 100%  MIPCA 10 100%  MCA 12 95% MCA  5%Butyl Acetate 17 90% MCA 10% Butyl Acetate 19 80% MCA 20% Butyl Acetate36 95% MCA  5% Ethyl Acetate 15 90% MCA 10% Ethyl Acetate 20 80% MCA 20%Ethyl Acetate 24 95% MCA  5% Ethyl Formate 13 90% MCA 10% Ethyl Formate17 80% MCA 20% Ethyl Formate 21 95% MCA  5% Methyl Acetate 13 90% MCA10% Methyl Acetate 17 80% MCA 20% Methyl Acetate 22 95% MCA  5% MethylEthyl Ketone 12 90% MCA 10% Methyl Ethyl Ketone 18 80% MCA 20% MethylEthyl Ketone 22 98% MIPCA  2% MIPCYA 26 95% MIPCA  5% MIPCYA 46 90%MIPCA 10% MIPCYA 48 95% MCA  5% Ethyl Acetoacetate 19 90% MCA 10% EthylAcetoacetate 19 90% MIPCA 10% MCYA 25 90% MIPCA 10% Methoxy propyl 46cyanoacetate (MPCYA) 90% MIPCA 10% BCYA 28

Example 10 Occluding Compositions Comprising Multiple Cyanoacrylateswith Degradation Evaluated

Solutions comprising various percentages of more than one cyanoacrylatewith or without an additive(s) were used. The same method as describedin Example 9 was utilized in this evaluation of degradation.

Fourteen Day Study

Cyanoacrylate Additive % Loss 70:30% MIPCA:MCA 11 70:30% MIPCA:MCA  5%PLGA 12 70:30% MIPCA:MCA 10% MCYC 18 70:30% MIPCA:MCA 20% MCYC 31 70:30%MIPCA:MCA 40% MCYC 51 50:50% MIPCA:MCA 10% MCYC 16 50:50% MIPCA:MCA 20%MCYC 25 50:50% MIPCA:MCA 40% MCYC 42 70:30% MIPCA:MCA 9 70:30% MPCA:nBCA13 70:30% MPCA:nBCA  2% Ethylene Carbonate 14 70:30% MPCA:nBCA  5%Ethylene Carbonate 16 70:30% MPCA:nBCA 10% Ethylene Carbonate 22 70:30%MPCA:nBCA 20% Ethylene Carbonate 32 50:50% MPCA:nBCA 12 50:50% MPCA:nBCA 2% Ethylene Carbonate 13 50:50% MPCA:nBCA  5% Ethylene Carbonate 1450:50% MPCA:NBCA 10% Ethylene Carbonate 17 50:50% MPCA:NBCA 20% EthyleneCarbonate 19 70:30% MPCA:MCA 14 70:30% MPCA:MCA  2% Ethylene Carbonate15 70:30% MPCA:MCA  5% Ethylene Carbonate 17 70:30% MPCA:MCA 10%Ethylene Carbonate 21 70:30% MPCA:MCA 20% Ethylene Carbonate 30 50:50%MPCA:MCA 16 50:50% MPCA:MCA  2% Ethylene Carbonate 15 50:50% MPCA:MCA 5% Ethylene Carbonate 20 50:50% MPCA:MCA 10% Ethylene Carbonate 2350:50% MPCA:MCA 20% Ethylene Carbonate 31 70:30% MIPCA:nBCA  2% EthyleneCarbonate 10 70:30% MIPCA:nBCA  5% Ethylene Carbonate 13 70:30%MIPCA:nBCA 10% Ethylene Carbonate 17 70:30% MIPCA:nBCA 20% EthyleneCarbonate 25 50:50% MIPCA:nBCA 6 50:50% MIPCA:nBCA  2% EthyleneCarbonate 7 50:50% MIPCA:nBCA  5% Ethylene Carbonate 11 50:50%MIPCA:nBCA 10% Ethylene Carbonate 12 50:50% MIPCA:nBCA 20% EthyleneCarbonate 22 80:20% MCA:MECA 13 50:50% MCA:MECA 16 80:20% MCA:MECA 1150:50% MCA:MECA 13

Example 11 Study of Ultrasound Visibility of Occluding Composition inModel

An occluding composition was introduced by 1 cc syringe to a channelsized to mimic the human fallopian tubes in an ultrasound phantom model.An ultrasound machine (manufactured by GE Medical Systems, model:Voluson 730Pro) was used to visualize the occluding composition. Theultrasound probe was positioned near the cured occluding compositionthat occupied the channel within the ultrasound phantom model. A clearimage of the resulting solid or semi-solid occluding composition wasvisible on the monitor, confirming the ability to view the occludingcomposition once cured in situ in a patient post delivery.

Example 12 Evaluation in Human Subjects

A delivery system comparable to that shown in FIG. 1 was used to deliveran occlusive material to the fallopian tubes of four human subjects, inaccordance with the rules of the institution's Institutional ReviewBoard. Once the occlusive material was delivered, placement wasconfirmed by using Ultrasound. An Ultrasound (manufactured by Philips,model: HD3) was performed transvaginally and the probe was positionedwhere the left and right cornua were visualized. A clear image of theresulting solid or semi-solid occluding composition was visible on themonitor, confirming the ability to view the occluding composition oncecured in situ in a patient post delivery. Subsequently, the subjectsunderwent a full hysterectomy procedure (removal of the uterus withfallopian tubes intact) for evaluation immediately following thedelivery of the occlusive material. Placement of the delivery system andocclusive material was performed with tactile feel and successfulplacement was confirmed by visual evaluation of the uterine cavity andfallopian tubes on an examination table once removed from the subject.Proper location of the occlusive material as visualized by ultrasoundwas confirmed by direct visualization of the dissected uterus andfallopian tubes.

REFERENCES

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FOREIGN PATENT DOCUMENTS WO 81/00701 WO 98/31308 WO 94/24944 WO 99/07297WO 94/28803 WO 99/47073 WO 97/12569 WO 00/44323 WO 97/49345 WO 00/24374WO 97/42987 WO 01/37760 WO 98/26737 WO 02/39880 WO 03/070085

OTHER PUBLICATIONS

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What is claimed is:
 1. A transcervical device, comprising, an introducershaft comprising an atraumatic tip and defining one opening proximatethe atraumatic tip for providing one catheter; the catheter comprisingan end structure on a delivery end for maintaining the delivery end inthe uterine cornua and aiding in localized delivery of a composition,attachment elements on a proximal end, and elements for providing thecomposition into and through the catheter.
 2. The transcervical deviceof claim 1, wherein the end structure is a cup, nozzle, or a balloon. 3.The transcervical device of claim 1, further comprising a deliverydevice stabilizer for holding the transcervical device in place oncepositioned.
 4. The transcervical device of claim 3, wherein the deliverydevice stabilizer fits over and attaches to the cervix of the patient orfits into or expands within the cervix to hold the device in position.5. The transcervical device of claim 1, wherein the catheter is a duallumen balloon catheter.
 6. The transcervical device of claim 1, furthercomprising a composition comprising an occlusive material.
 7. Atranscervial device, comprising, an introducer shaft having a closed tipfor contacting the fundus of a uterus and having one exit port proximatethe closed tip for providing one catheter; and one catheter, comprisingat the delivery end an end structure that aids in localized delivery ofa composition to the tubal ostia of a fallopian tube, wherein the endstructure is a cup, nozzle, or balloon.
 8. The transcervical device ofclaim 7, further comprising means for providing the composition into andthrough the catheter.
 9. The transcervical device of claim 7, furthercomprising a delivery device stabilizer for holding the transcervicaldevice in place once positioned.
 10. The transcervical device of claim9, wherein the delivery device stabilizer fits over or attaches to thecervix of the patient or fits into or expands within the cervix to holdthe device in position.
 11. The transcervical device of claim 7, whereinthe catheter is a dual lumen balloon catheter.
 12. The transcervicaldevice of claim 7, further comprising a composition comprising anocclusive material.